196 | id == 196
196 | category_id == 18
196 | category_order == 15
196 | category_name == Weight
196 | category_color == #C47AC0
196 | slug == MC4R-obesity-leptin
196 | title == The Genetic Link Between Appetite and Obesity (MC4R)
196 | meta_description == MC4R encodes a receptor with crucial roles in appetite control. Learn about its variants associated with obesity and body fat.
196 | summary == <p style="text-align:justify"><strong><em>MC4R</em> encodes a receptor with crucial roles in appetite control. Multiple variants near this gene have a robust association with obesity and body composition &mdash; read on to check your genes and get tailored tips.</strong></p>
196 | overall_score_text == Your Obesity Score (Based on MC4R Gene)
196 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/MC4R--Weight.jpg
196 | author_id == 9
196 | author_name == Aleksa Ristic
196 | author_title == MS (Pharmacy)
196 | author_order == 45
196 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Aleksa.jpg
196 | author_intro == <p><strong>Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.</strong>&nbsp;&nbsp;</p>    <p>Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions&mdash;writing and health&mdash;and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.</p>
196 | reviewer == None
196 | medical_reviewer_id == 11
196 | medical_reviewer_name == Puya Yazdi
196 | medical_reviewer_title == MD
196 | publish_date == 2020
196 | publish_date == 5
196 | publish_date == 22
196 | avg_rating == 5.0
196 | tags_id == 455
196 | tags_name == Alpha-MSH
196 | tags_id == 200
196 | tags_name == Appetite
196 | tags_id == 297
196 | tags_name == Dietary fat
196 | tags_id == 201
196 | tags_name == Food Cravings
196 | tags_id == 317
196 | tags_name == High-protein diet
196 | tags_id == 456
196 | tags_name == Leptin
196 | tags_id == 457
196 | tags_name == MC4R Gene
196 | tags_id == 141
196 | tags_name == Metabolic Health
196 | tags_id == 165
196 | tags_name == Obesity
196 | tags_id == 245
196 | tags_name == Sunlight
196 | tags_id == 184
196 | tags_name == Weight Loss
196 | permissions_favorite == False
196 | permissions_rate == False
196 | content_article == <p><em><span style="font-weight: 400;">This article is for informational purposes only. None of the information here should be taken as medical advice. If you are struggling to maintain a healthy weight, seek medical help. </span></em><em><span style="font-weight: 400;">Keep in mind that these results are based on association studies, which are correlative and aren&rsquo;t necessarily causative. Any single genetic variant will typically contribute only a small proportion to the overall risk of the condition, and non-genetic factors play a large role in developing a condition as well. Therefore, just because you have one of these genotypes does not necessarily mean you are at an increased risk of developing this condition!</span></em></p> <h2><strong>What is MC4R?</strong></h2> <p><span style="font-weight: 400;">The </span><a href="../../../gene/mc4r/"><em><span style="font-weight: 400;">MC4R</span></em></a><span style="font-weight: 400;"> gene encodes the melanocortin 4 (MC4) receptor, which binds alpha-melanocyte-stimulating hormone or </span><a href="http://selfhacked.com/blog/alpha-msh-its-role-in-weight-control-autoimmunity-cirs-and-cfs/"><span style="font-weight: 400;">a-MSH</span></a><span style="font-weight: 400;">. The primary location of this receptor is the brain, more precisely the </span><a href="https://selfhacked.com/blog/hypothalamus-101/"><span style="font-weight: 400;">hypothalamus</span></a><span style="font-weight: 400;">, where it controls food intake, metabolism, reproductive behavior, and more [</span><a href="https://ghr.nlm.nih.gov/gene/MC4R"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><strong>MC4R in Weight Control</strong></h3> <p><a href="https://www.researchgate.net/figure/The-leptin-melanocortin-pathway-POMC-neurons-in-the-arcuate-nucleus-are-activated-by_fig1_303707219" target="_blank" rel="noopener"><strong><img src="https://www.researchgate.net/publication/303707219/figure/fig1/AS:567070296416256@1512211502738/The-leptin-melanocortin-pathway-POMC-neurons-in-the-arcuate-nucleus-are-activated-by.png" alt="The leptin-melanocortin pathway. POMC neurons in the arcuate nucleus are activated by leptin and produce the &alpha;-melanocyte stimulating hormone (&alpha;-MSH), which then activates the MC4R receptor." width="607" height="494" /></strong></a></p> <p><sub><span style="font-weight: 400;">Source: Huvenne et al. (2016), Rare Genetic Forms of Obesity: Clinical Approach and Current Treatments in 2016</span></sub></p> <p><span style="font-weight: 400;">The MC4 receptor is a part of the leptin-melanocortin pathway in the hypothalamus. <a href="http://selfhacked.com/blog/all-about-leptin-its-role-in-chronic-inflammation-cfs-and-weight/">Leptin</a> is a crucial hormone for appetite and weight control, released by fat tissue. When fat stores are adequate, leptin suppresses appetite by stimulating the production of a-MSH (see the image). On the other hand, low leptin reduces MC4R activity and thus promotes energy intake [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17578380"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Even though leptin suppresses appetite and stimulates energy expenditure, excess levels are typical in obese people. Over-secretion leads to </span><a href="https://selfhacked.com/blog/the-root-causes-of-leptin-resistance-and-12-ways-to-reverse-it/"><span style="font-weight: 400;">leptin resistance</span></a><span style="font-weight: 400;">, a condition in which leptin loses the ability to reduce food intake via melanocortins [</span><a href="https://pubmed.ncbi.nlm.nih.gov/17021377/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><em><span style="font-weight: 400;">MC4R</span></em><span style="font-weight: 400;"> is the most studied gene when it comes to obesity. Reduced activity of the MC4 receptor is the most common genetic cause of obesity, mediated by increased food intake [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10903343/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12646665/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><strong><em>Did you know?</em></strong><span style="font-weight: 400;"> MC4R deficiency might have played a crucial role in our evolution. People with mutations that impaired MC4R function were prone to overeating, which likely brought them an evolutionary advantage during food shortages. However, now that food is abundant for the majority, these mutations are showing their other face and contributing to obesity [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17628007"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Besides food intake, </span><em><span style="font-weight: 400;">MC4R</span></em><span style="font-weight: 400;"> can also impact weight control via </span><a href="https://selfhacked.com/blog/glucose/"><span style="font-weight: 400;">glucose</span></a><span style="font-weight: 400;"> and fat metabolism and growth stimulation [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12646665/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The MC4R gene encodes the melanocortin 4 receptor, which regulates food intake, metabolism, and more. In conjunction with leptin, it plays a key role in appetite and weight control.</span></p> <h2><strong>MC4R Variants and Body Weight Measurements</strong></h2> <h3><strong>Rs17782313</strong></h3> <h4><strong>Obesity</strong></h4> <p><a href="../../snp/rs17782313/"><span style="font-weight: 400;">Rs17782313</span></a><span style="font-weight: 400;"> is the most studied SNP near the MC4R gene when it comes to obesity. In a huge meta-analysis of 61 studies and over 300,000 subjects, the "C" allele was associated with 18% higher obesity rates. The results were consistent across different ages and ethnic groups (European/Asian) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3458070/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a meta-analysis of 77,200 European adults, each "C" allele was associated with a 0.22 increase in BMI, 8% higher chances of being overweight (BMI &ge; 25), and 12% of being obese (BMI &ge; 30). The same analysis found 30% higher obesity rates among 10,500 children, suggesting they might be more sensitive to MC4R variants than adults [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669167/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A study of 8,400 subjects confirmed a link between this SNP and obesity in European children but not in African American children [<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860794/">R</a>]. </span></p> <h4><strong>Eating Habits</strong></h4> <p><span style="font-weight: 400;">Among 18,600 participants from different European countries, rs17782313-C was associated with increased hunger, snacking, and eating large amounts of food [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19153581/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a study of 5,724 women, this variant correlated with higher intakes of calories and dietary fat [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2572696/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A review of clinical trials confirmed the link between rs17782313 and the above eating habits but found no influence on emotional eating [<a href="https://pubmed.ncbi.nlm.nih.gov/23147118/" target="_blank" rel="noopener">R</a>].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The &ldquo;C&rdquo; allele at rs17782313 is associated with obesity, likely due to unhealthy snacking and increased intake of total calories and dietary fat.</span></p> <h3><strong>Rs6567160</strong></h3> <p><span style="font-weight: 400;">In a meta-analysis of over 100,000 people from different ethnic groups, the &ldquo;C&rdquo; allele at </span><a href="../../snp/rs6567160/"><span style="font-weight: 400;">rs6567160</span></a><span style="font-weight: 400;"> correlated with [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740398/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">A higher percentage of body fat</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Lower </span><a href="https://www.selfhacked.com/blog/hdl-cholesterol/"><span style="font-weight: 400;">HDL</span></a><span style="font-weight: 400;"> cholesterol</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Increased diabetes rates</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Leptin resistance&nbsp;</span></li> </ul> <p><span style="font-weight: 400;">The same variant showed a link with body mass index (BMI) in another study of 28,600 participants [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3888264/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><strong>Rs12970134</strong></h3> <p><span style="font-weight: 400;">In a meta-analysis of 34,400 people, predominantly from European countries, the &ldquo;A&rdquo; allele at </span><a href="../../snp/rs12970134/"><span style="font-weight: 400;">rs12970134</span></a><span style="font-weight: 400;"> was associated with higher BMI. Among 14,600 Europeans and Indian Asians, this variant showed a link with waist circumference and </span><a href="https://www.selfhacked.com/blog/top-tips-for-fixing-insulin-resistance/"><span style="font-weight: 400;">insulin resistance</span></a><span style="font-weight: 400;">. People with the &ldquo;AA&rdquo; genotype had approximately 2 cm higher waist circumference [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19079260"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18454146"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The same SNP correlated with 21% higher odds of being overweight or obese in a trial of 2,179 Chinese children and adolescents. However, the impact was significant only in children who had &lt;1 hour of physical activity and &gt;2 hours of sitting daily [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5231371/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Among 151 Chinese children and their parents, those with rs12970134-A were more easily attracted by food, and they consumed more beverages [<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433775/" target="_blank" rel="noopener">R</a>].</span></p> <h3><strong>Rs2229616</strong></h3> <p><span style="font-weight: 400;">One meta-analysis summarized 37 studies involving over 55,000 subjects from different ethnic groups. According to the results, the &ldquo;T&rdquo; allele at </span><a href="../../snp/rs2229616/"><span style="font-weight: 400;">rs2229616</span></a><span style="font-weight: 400;"> correlates with significantly lower obesity rates [</span><a href="https://pubmed.ncbi.nlm.nih.gov/19696756/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400; background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Rs6567160-C and rs12970134-A correlate with higher and rs2229616-T with lower obesity rates.</span></p> <h3><strong>How It Works</strong></h3> <p><span style="font-weight: 400;">As mentioned, MC4R is essential for appetite control. The above studies have confirmed increased energy intake, especially from high-calorie food and unhealthy snacks, as the primary cause of weight gain [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12646666"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Mice without MC4R are prone to obesity and overeating. Obesity-associated MC4R mutations reduce gene expression and hinder the binding of </span><a href="http://selfhacked.com/blog/alpha-msh-its-role-in-weight-control-autoimmunity-cirs-and-cfs/"><span style="font-weight: 400;">alpha-MSH</span></a><span style="font-weight: 400;">. Hence, the discussed SNPs likely reduce MC4R expression or activity, although functional tests haven&rsquo;t confirmed this yet [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16274851"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12851297"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669167/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The activation of MC4 receptors triggered by high leptin levels is the primary &ldquo;satiety signal&rdquo; (a signal to stop eating). In mice without these receptors, leptin is unable to reduce appetite [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16274851"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In lab animals, chronic activation of the MC4 receptors reduced abdominal fat and improved glucose metabolism, suggesting another crucial metabolic role of MC4R [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/11581309"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The discussed MC4R variants likely reduce gene expression or receptor activity, thus increasing food intake and hindering glucose and fat metabolism.</span></p> <h3><strong>Limitations</strong></h3> <p><span style="font-weight: 400;">Different SNPs near the MC4R gene have shown a robust link with obesity in diverse populations, but the evidence is less consistent in African Americans. Additionally, this genetic effect seems to peak in childhood and decline with age [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860794/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16274851"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Even though MC4R has one of the strongest genetic effects on body weight measures, the discussed SNPs contribute to only ~0.14% of variations in BMI and ~0.26% of variations in fat mass [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669167/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h2><strong>Your MC4R Results for Obesity and Food Intake</strong></h2> <p>*5946760420820885*</p> <h3><strong>SNP Summary</strong></h3> <p><strong>Primary SNP:</strong></p> <p><strong><em>MC4R</em></strong> <a href="../../snp/rs17782313/"><strong>rs17782313</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = associated with obesity, snacking, and overeating</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = not associated with obesity or food intake</span></li> </ul> <p><strong>Other Important SNPs:</strong></p> <p><strong><em>MC4R</em></strong> <a href="../../snp/rs6567160/"><strong>rs6567160</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = associated with obesity and higher body fat percentage&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = not associated with obesity or body fat</span></li> </ul> <p><strong><em>MC4R</em></strong> <a href="../../snp/rs12970134/"><strong>rs12970134</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = associated with obesity and increased waist circumference&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = not associated with obesity</span></li> </ul> <p><strong><em>MC4R</em></strong> <a href="../../snp/rs2229616/"><strong>rs2229616</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = associated with lower obesity rates</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = not associated with obesity</span></li> </ul> <h4><strong>Population Frequency</strong></h4> <p><span style="font-weight: 400;">The first three variants are usually inherited together in European populations, which means they act as a single genetic factor. Around 36-39% of European descendants carry one copy, and 6-7% carry both copies of the problematic alleles (C, C, and A, respectively).</span></p> <p><span style="font-weight: 400;">When it comes to rs2229616, only around 3% of the general population carries the protective &ldquo;T&rdquo; allele. It&rsquo;s even less common among Europeans (1.5%).</span></p> <p>*7456913273399408*</p> <p>&nbsp;</p> <h2><strong>Recommendations to Improve Weight Control</strong></h2> <p><em><span style="font-weight: 400;">You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for you. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.</span></em></p> <p>*2261115805193312*</p> <h3><strong>Lifestyle</strong></h3> <h4><strong>Improve Sleep Quality</strong></h4> <h5><strong>Circadian Rhythm</strong></h5> <p><span style="font-weight: 400;">In one study, animals in a constant light cycle had lower alpha-MSH levels, which suggests</span> <a href="http://selfhacked.com/blog/what-it-means-to-keep-to-a-circadian-rhythm/"><span style="font-weight: 400;">circadian rhythm</span></a><span style="font-weight: 400;"> problems may result in less MSH. On the other hand, moderate light (UV) exposure during the day can boost MSH and activate melanocortin receptors [</span><a href="http://www.ncbi.nlm.nih.gov/m/pubmed/10816644/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://link.springer.com/article/10.1007%2Fs00403-011-1183-3"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/7357442"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Impaired circadian rhythm is associated with leptin resistance and </span><a href="https://selfhacked.com/blog/132-biological-mechanisms-for-weight-modulation/"><span style="font-weight: 400;">obesity</span></a><span style="font-weight: 400;"> in animals [</span><a href="http://www.cell.com/cell-metabolism/abstract/S1550-4131(15)00272-7"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Research over the past few decades has recognized the importance of circadian biology in obesity, energy balance, and metabolism [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4013188/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A disrupted circadian rhythm may be why shift workers seem to be at an increased risk of obesity [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/20122305"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h5><strong>Sleep Duration</strong></h5> <p><span style="font-weight: 400;">In one trial, restful </span><a href="https://selfhacked.com/blog/health-benefits-sleep/"><span style="font-weight: 400;">sleep</span></a><span style="font-weight: 400;"> in non-obese individuals (8+ of uninterrupted sleep) normalized leptin levels. On the other hand, sleep deprivation can decrease leptin and prevent MC4R activation [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15531540"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24732925"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Short sleep duration correlated with weight gain in several studies. Scientists think that poor sleep may increase </span><a href="https://selfhacked.com/blog/top-10-ways-to-curb-your-hunger-and-approaches-that-didnt-work/"><span style="font-weight: 400;">hunger</span></a><span style="font-weight: 400;"> and cravings and disrupt appetite-controlling hormones like </span><a href="https://selfhacked.com/blog/ghrelin-role-cognitive-gut-function-weight-inflammation-autoimmunity/"><span style="font-weight: 400;">ghrelin</span></a><span style="font-weight: 400;"> and leptin [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18239586"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973603/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2398753/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1547-5069.2009.01262.x/full"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.0010062"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Circadian rhythm disturbance and sleep deprivation may reduce MC4 receptor stimulation and contribute to negative changes in weight control and metabolism.</span></p> <h4><strong>Moderate Sun Exposure</strong></h4> <p><span style="font-weight: 400;">Moderate </span><a href="https://selfhacked.com/blog/avoiding-sun-will-kill-14-proven-science-based-health-benefits-sun/"><span style="font-weight: 400;">sun/UV exposure</span></a><span style="font-weight: 400;"> during the day may boost a-MSH and activate melanocortin receptors [</span><a href="http://link.springer.com/article/10.1007%2Fs00403-011-1183-3"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://www.ncbi.nlm.nih.gov/pubmed/7357442"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><a href="http://selfhacked.com/blog/35proven-health-benefits-vitamin-d-part-1/"><span style="font-weight: 400;">Vitamin D</span></a><span style="font-weight: 400;"> deficiency might contribute to obesity in some cases. Sun exposure supplies vitamin D and may also help prevent obesity in animals, regardless of their vitamin D status [</span><a href="https://www.sciencedirect.com/science/article/pii/S0306987708005288"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25342734"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In one study, intense light exposure, particularly in the morning, was associated with a lower BMI, independent of sleep duration and timing [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3973603/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Exposure to at least 45 minutes of morning light (6-9 am) for three weeks in obese women reduced body fat and appetite. Although encouraging, more research is needed to verify the link between sunlight exposure and </span><a href="http://selfhacked.com/blog/a-comprehensive-list-of-effective-ways-to-lose-weight/"><span style="font-weight: 400;">weight loss</span></a><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23429094/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Moderate sun exposure may activate your MC4 receptors and supply vitamin D, both of which are important for weight and appetite control.<br /></span></p> <h4><strong>Limit Alcohol Intake</strong></h4> <p><span style="font-weight: 400;">In different animal studies, chronic alcohol exposure reduced the levels of a-MSH, the primary activator of MC4 receptors [</span><a href="http://www.ncbi.nlm.nih.gov/pubmed/23792540"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/6263780/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/2943358/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18162070/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Alcohol is a significant source of calories, delivering 7 kcal per gram. Although light-to-moderate alcohol consumption is unlikely to impact weight gain, heavy drinking has a robust link with obesity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338356/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In two studies of over 11,600 participants, increased alcohol consumption was associated with abdominal obesity, which is a strong risk factor for heart disease [</span><a href="https://pubmed.ncbi.nlm.nih.gov/17885722/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2984859/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4756331/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Alcohol abuse may suppress MC4 receptors and contribute to weight gain and abdominal obesity.</span></p> <h3><strong>Diet</strong></h3> <h4><strong>Consume More Protein and Less Fat</strong></h4> <p><span style="font-weight: 400;">Mice lacking the MC4R gene don&rsquo;t experience appetite reduction and fat burning in response to high-fat diets. Likewise, people with the discussed variants have increased intake of total energy and dietary fat, along with impaired metabolism [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12686465"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/14551222/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">It's essential to control your daily calories if you carry the problematic alleles and are struggling to maintain a healthy weight. You may also want to reduce the intake of dietary fat.</span></p> <p><span style="font-weight: 400;">Dietary protein contains much fewer calories per gram than fat (4 vs. 9 kcal). It can improve leptin sensitivity, which makes it a perfect fat replacement for people with MC4R variants [</span><a href="http://ajcn.nutrition.org/content/82/1/41.full"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26797090/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Research suggests that getting more calories from protein may support weight loss, metabolism, and satiety (fullness). Complex carbs may also be a healthy fat substitute, but make sure to avoid refined grains and low-fat products with added starch and sugar [</span><a href="http://ajcn.nutrition.org/content/82/1/41.abstract"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10193874"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10375057"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">To lessen the impact of your MC4R variants, limit the intake of total calories and dietary fat, and consume more protein and complex carbs.</span></p> <h4><strong>Avoid Unhealthy Snacks</strong></h4> <p><span style="font-weight: 400;">Cutting out unhealthy snacks is one of the biggest steps toward weight loss. That&rsquo;s essential for people with MC4R variants, given their affinity to high-calorie snacks [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860794/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/19153581/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Processed, calorie-dense snacks can significantly impair weight control. Among 6,500 US adolescents, those who were obese and overweight snacked more frequently and consumed more calories from snacks. A study of 400 Italian children came to a similar conclusion [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22117666/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682988/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24897170/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Soups and other liquid meals may be an excellent replacement for snacks. Research suggests that eating the same food made in a soup (instead of as solid food) improves satiety and reduces calorie intake [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/10500012/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2128765/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Among 200 overweight and obese women, those who ate soup lost 50% more weight than those who ate an energy-dense snack [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15976148"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Processed, calorie-dense snacks can impair weight control in people with MC4R variants. Consider replacing them with soups, fruit, or other low-calorie options.</span></p> <h4><strong>Spicy Food</strong></h4> <p><span style="font-weight: 400;">Spicy foods containing </span><a href="http://selfhacked.com/blog/capsaicin/"><span style="font-weight: 400;">capsaicin</span></a><span style="font-weight: 400;">, such as chili and cayenne peppers, helped reduce appetite and improve weight control in different clinical trials [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/13129472"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22378725"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/15611784"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3699483/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Capsaicin may be particularly beneficial for people with MC4R SNPs due to its potential to reduce leptin resistance. However, the research in this area is limited [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088424/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h3><strong>Supplements</strong></h3> <h4><strong>Berberine</strong></h4> <p><a href="http://selfhacked.com/blog/19-health-benefits-of-berberine-with-references/"><span style="font-weight: 400;">Berberine</span></a><span style="font-weight: 400;"> is an alkaloid with potent metabolic effects. People use berberine as a supplement to support weight control and glucose metabolism.</span></p> <p><span style="font-weight: 400;">Berberine supplementation reduced BMI and enhanced leptin sensitivity in 37 patients with metabolic syndrome. In another study, it caused an average weight loss of 5 lbs (2,3 kg) and lowered blood lipids [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310165/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22739410"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">According to a 2020 review of human and animal studies, berberine might contribute to weight loss by improving </span><a href="https://selfhacked.com/blog/how-your-gut-microbiota-can-make-you-fat-or-thin/"><span style="font-weight: 400;">gut microbiota</span></a><span style="font-weight: 400;"> and glucose and fat metabolism [</span><a href="https://pubmed.ncbi.nlm.nih.gov/32353823/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Due to its effects on metabolism and leptin sensitivity, berberine may be the right choice for people with MC4R SNPs. However, the available research is inconclusive.</span></p>
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196 | content_learn_more_7456913273399408_text == Based on the variants we looked at, your MC4R gene is associated with slightly higher obesity rates. However, this doesn't necessarily reflect your overall risk of obesity, just one gene related to it. Reduce fat intake and improve sleep quality to maintain a healthy weight. Keep reading to find out more.
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rsIDs = rs17782313,rs6567160,rs12970134,rs2229616
rsStatus = rs17782313,,chr18,60183864,T,A,C,,23,0,Normal
rsStatus = rs6567160,,chr18,60161902,T,C,,,15,8,HET
rsStatus = rs12970134,,chr18,60217517,G,A,,,22,12,HET
rsStatus = rs2229616,MC4R,chr18,60372043,C,T,,,45,0,Normal
