219 | id == 219
219 | category_id == 18
219 | category_order == 15
219 | category_name == Weight
219 | category_color == #C47AC0
219 | slug == PCSK1-obesity-appetite
219 | title == How Genes Influence Appetite & Obesity (PCSK1)
219 | meta_description == PCSK1 encodes an enzyme with crucial roles in appetite and metabolism. Click to learn about its link with obesity.
219 | summary == <p style="text-align:justify"><strong>The <em>PCSK1</em> gene encodes an enzyme with crucial roles in appetite and metabolism. Specific variants in this gene correlate with obesity &mdash; read on to learn the details and check your genes.</strong></p>
219 | overall_score_text == Your Obesity Score (Based on PCSK1)
219 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/PCSK1--Weight.jpg
219 | author_id == 9
219 | author_name == Aleksa Ristic
219 | author_title == MS (Pharmacy)
219 | author_order == 45
219 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Aleksa.jpg
219 | 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>
219 | reviewer == None
219 | medical_reviewer_id == 11
219 | medical_reviewer_name == Puya Yazdi
219 | medical_reviewer_title == MD
219 | publish_date == 2020
219 | publish_date == 6
219 | publish_date == 17
219 | avg_rating == 5.0
219 | tags_id == 455
219 | tags_name == Alpha-MSH
219 | tags_id == 200
219 | tags_name == Appetite
219 | tags_id == 186
219 | tags_name == BMI
219 | tags_id == 465
219 | tags_name == Dietary protein
219 | tags_id == 207
219 | tags_name == Exercise
219 | tags_id == 471
219 | tags_name == Hunger
219 | tags_id == 139
219 | tags_name == Insulin
219 | tags_id == 456
219 | tags_name == Leptin
219 | tags_id == 165
219 | tags_name == Obesity
219 | tags_id == 497
219 | tags_name == PCSK1 gene
219 | tags_id == 496
219 | tags_name == POMC
219 | tags_id == 184
219 | tags_name == Weight Loss
219 | permissions_favorite == False
219 | permissions_rate == False
219 | 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 PCSK1?</strong></h2> <p><span style="font-weight: 400;">The </span><a href="../../../gene/pcsk1/"><span style="font-weight: 400;">PCSK1</span></a><span style="font-weight: 400;"> gene helps produce proprotein convertase 1/3 (PC1/3), an enzyme abundant in the brain and endocrine system. PC1/3 activates a range of hormones and peptides involved in [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082390/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://ghr.nlm.nih.gov/gene/PCSK1"><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;">Temperature control</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Nutrient absorption</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Appetite and feeding behavior</span></li> <li style="font-weight: 400;"><a href="https://selfhacked.com/blog/glucose/"><span style="font-weight: 400;">Glucose</span></a><span style="font-weight: 400;"> and fat metabolism</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Energy expenditure</span></li> </ul> <p><span style="font-weight: 400;">Given the crucial role of PCSK1 in the above processes, variants in this gene correlate with various health conditions, including diabetes, malabsorption, obesity, and thyroid disorders [</span><a href="https://academic.oup.com/edrv/article/37/4/347/2567098"><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;">PCSK1 encodes an enzyme (PC1/3) with complex roles in metabolism. Variants in this gene correlate with obesity, hormonal disorders, and malabsorption.</span></p> <h3><strong>PCSK1 in Weight Control</strong></h3> <p><span style="font-weight: 400;">PCSK1 was among the first discovered genes with a role in severe hereditary obesity. It&rsquo;s the third most common contributor to obesity caused by a single gene (monogenic) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22210313/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/24396277/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">PCSK1-deficient mice quickly develop obesity due to uncontrolled food intake. Likewise, mutations in this gene cause early-onset obesity in humans, despite severe diarrhea and malabsorption [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16644867/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/9207799/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3719133/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><strong>Crucial Roles in Appetite</strong></h4> <p><span style="font-weight: 400;">Animal and clinical research has identified overeating as the primary cause of PCSK1-associated obesity [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16644867/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/23562752/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/17595246/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The PC1/3 enzyme is crucial in 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 activates an array of peptides involved in food intake and metabolism. It turns </span><a href="../../article/pomc-weight-209"><span style="font-weight: 400;">POMC</span></a><span style="font-weight: 400;"> into </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;">, a powerful appetite-suppressing hormone [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21805247/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8380577/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">By activating the </span><a href="../../article/mc4r-obesity-leptin-196"><span style="font-weight: 400;">MC4R</span></a><span style="font-weight: 400;"> receptors, a-MSH reduces food intake, stimulates energy expenditure, and improves glucose metabolism [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/22211889/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Mice and humans lacking PC1/3 have impaired POMC activation and lower a-MSH levels in the hypothalamus [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/16644867/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/9207799/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <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"><span style="font-weight: 400;"><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 in the paraventricular nucleus resulting in a satiety signal. A separate group of neurons expressing NPY and AGRP produce molecules that act as potent inhibitors of MC4R signaling. The downstream roles of SIM1, BDNF, and TKRB are currently being explored. AGRP = agouti-related protein; BDNF = brain-derived neurotropic factor; LEPR = leptin receptor; NPY = neuropeptide Y; POMC = proopiomelanocortin; SIM1 = single-minded 1; TRKB = tyrosine kinase receptor.&nbsp;" width="581" height="473" /></span></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 mechanism described and illustrated above belongs to the leptin-melanocortin pathway, the master controller of appetite and energy balance [</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="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">PC1/3 plays a crucial role in the leptin-melanocortin pathway by turning POMC into alpha-MSH. This pathway suppresses appetite, boosts metabolism, and stimulates energy expenditure.</span></p> <h4><strong>Other Pathways</strong></h4> <p><span style="font-weight: 400;">PC1/3 activates many other hormones involved in energy balance and metabolism. It enables glucose metabolism by turning proinsulin into active </span><a href="https://selfhacked.com/blog/insulin-101/"><span style="font-weight: 400;">insulin</span></a><span style="font-weight: 400;">. Not surprisingly, common variants in the PCSK1 gene have been associated with diabetes and impaired insulin levels [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/12145326/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5323889/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3557230/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">PCSK1-associated obesity most likely results from a combination of [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6082390/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li><strong>Increased appetite</strong></li> <li><span style="font-weight: 400;">Reduced energy expenditure</span></li> <li><span style="font-weight: 400;">Impaired glucose metabolism</span></li> </ul> <h2><strong>The Link Between PCSK1 Variants and Obesity</strong></h2> <p><span style="font-weight: 400;">PCSK1 is one of the most studied genes when it comes to obesity. A huge meta-analysis gathered data from over 330K people and confirmed a significant link between three PCSK1 variants and obesity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498155/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]:</span></p> <ul> <li style="font-weight: 400;"><a href="../../../snp/rs6232/"><span style="font-weight: 400;">rs6232</span></a><span style="font-weight: 400;">: people with the less common &ldquo;C&rdquo; allele had 15% higher obesity rates</span></li> <li style="font-weight: 400;"><a href="../../../snp/rs6234/"><span style="font-weight: 400;">rs6234</span></a><span style="font-weight: 400;">/</span><a href="../../../snp/rs6235/"><span style="font-weight: 400;">rs6235</span></a><span style="font-weight: 400;">: people with the less common &ldquo;C/G&rdquo; alleles had 7% higher obesity rates</span></li> </ul> <p><span style="font-weight: 400;">The second and third SNP are always inherited together, so the authors presented them as a pair.</span></p> <p><span style="font-weight: 400;">The SNPs had a higher impact among children, with 53% and 15% higher obesity rates for rs6232 and rs6234/rs6235, respectively. They were significant only in European (Caucasian) descendants, which made the vast majority of total subjects [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4498155/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Another large meta-analysis of 19 trials and over 200K participants came to a similar conclusion. It observed 19% higher odds of obesity for rs6232 and 9% for rs6234/rs6235 [</span><a href="https://pubmed.ncbi.nlm.nih.gov/25355447/"><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 4,174 subjects from China and Taiwan, rs6234/rs6235 were associated with a higher body-mass index (BMI) and waist circumference (WC) but only in men [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871798/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24140494/"><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;">Rs6232 and rs6234/rs6235 are associated with obesity among European descendants, especially children. Rs6234/rs6235 may correlate with obesity in East Asian men.<span style="font-weight: 400;">&nbsp;</span></span></p> <h3><strong>How It Works</strong></h3> <p><span style="font-weight: 400;">As mentioned, mutations that reduce PCSK1 activity may contribute to increased appetite and impaired metabolism. The above variants have a much milder impact on the gene functioning, but they can still mimic these changes to a lesser extent.</span></p> <p><span style="font-weight: 400;">The "C" allele at rs6232 changes one amino acid in the PC1/3 structure, hindering the production of this enzyme and reducing its activity by 30%. It lies right next to a mutation that causes obesity and overeating in mice [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26207343/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060179/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">On the other hand, rs6234 and rs6235 cause changes in the enzyme region responsible for proper folding and recognition of target hormones. Scientists haven't yet identified the functional consequences of these SNPs, but they likely impair enzyme activity in some way [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/8034588/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18604207/"><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;">Obesity-associated PCSK1 variants may impair enzyme activity, secretion, or recognition of hormones. Rs6232-C reduces enzyme activity by up to 30%.</span></p> <h2><strong>Your PCSK1 Results for Obesity</strong></h2> <p>*9369247560643995*&nbsp;</p> <h3><strong>SNP Summary and Table</strong></h3> <p><strong>Primary SNP:</strong></p> <p><strong><em>PCSK1</em></strong> <a href="../../../snp/rs6232/"><strong>rs6232</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = associated with higher obesity rates</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = not associated with obesity</span></li> </ul> <p><em><span style="font-weight: 400;">Population Frequency:</span></em><span style="font-weight: 400;"> Only around 6,5% of European descendants carry the &ldquo;C&rdquo; allele. It&rsquo;s a bit more common in South Asian populations (10%) and much less common in East Asian and African populations (0.5%).</span></p> <p><strong>Other Important SNPs:</strong></p> <p><strong><em>PCSK1</em></strong> <a href="../../../snp/rs6234/"><strong>rs6234</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = associated with obesity and higher 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>PCSK1</em></strong> <a href="../../../snp/rs6235/"><strong>rs6235</strong></a></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = associated with obesity and higher waist circumference&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = not associated with obesity</span></li> </ul> <p><em><span style="font-weight: 400;">Population Frequency</span></em><span style="font-weight: 400;">: These two SNPs are always inherited together, which means they act as a single genetic factor. Around 38,5% of Europeans carry one copy and 7% carry both copies of the minor alleles (C and G, respectively). They are more common in East Asians (57%) and less common in Africans (33%).</span></p> <p>*6900898855823863*</p> <p>&nbsp;</p> <h2><strong>Recommendations to Curb Hunger and Lose Weight</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>*3121532507733717*</p> <h3><strong>Lifestyle</strong></h3> <h4><strong>Exercise</strong></h4> <p><a href="https://selfhacked.com/blog/top-14-proven-health-benefits-exercise-references-mechanisms/"><span style="font-weight: 400;">Exercise</span></a><span style="font-weight: 400;"> activates POMC neurons in the hypothalamus, especially those with leptin receptors. In other words, it may compensate for poor POMC activation caused by your variants [</span><a href="https://www.sciencedirect.com/science/article/pii/S2212877818308706"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Resistance training is probably the best strategy to </span><a href="http://selfhacked.com/blog/a-comprehensive-list-of-effective-ways-to-lose-weight/"><span style="font-weight: 400;">lose weight</span></a><span style="font-weight: 400;">. It promotes fat burning and boosts </span><a href="../../article/boost-plasticity-with-the-bdnf-gene-50"><span style="font-weight: 400;">BDNF</span></a><span style="font-weight: 400;">, </span><a href="https://selfhacked.com/blog/endorphins/"><span style="font-weight: 400;">endorphins</span></a><span style="font-weight: 400;">, and other beneficial hormones that suppress appetite, improve mental health, and more [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/5124188"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://journal.frontiersin.org/article/10.3389/neuro.24.005.2010/full"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="http://www.news-medical.net/news/20120717/Mu-opioid-receptors-put-brakes-on-appetite.aspx"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Aerobic exercise (walking, running, swimming, etc.) has also caused significant reductions in belly fat in multiple studies [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/17637702"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21951360"><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;">Exercise regularly to overcome your PCSK1 variants, stimulate fat burning, and improve overall health.</span></p> <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 </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;"> 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 worsen the impact of PCSK1 SNPs. On the other hand, moderate light exposure during the day can boost a-MSH and activate MC4 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 </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;"> and obesity 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 suppress the leptin-melanocortin pathway [</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 worsen the impact of your SNPs and contribute to adverse changes in weight control, appetite, and metabolism.</span></p> <h4><strong>Avoid BPA-Containing Plastic</strong></h4> <p><span style="font-weight: 400;">Bisphenol-A (BPA) is a well-known endocrine disruptor found in plastic. It can impair the metabolism in fat cells by reducing the expression of PCSK1, among others [</span><a href="https://pubmed.ncbi.nlm.nih.gov/25878060/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A solid body of preclinical and clinical evidence has identified BPA as an environmental toxin associated with obesity and different endocrine disorders [</span><a href="https://pubmed.ncbi.nlm.nih.gov/28622415/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359373/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3306519/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]. If you are using plastics, make sure they are </span><strong>BPA-free</strong><span style="font-weight: 400;">.</span></p> <h3><strong>Diet</strong></h3> <h4><strong>Increase Protein Intake</strong></h4> <p><span style="font-weight: 400;">Dietary protein can reduce appetite and stimulate the leptin-melanocortin pathway, which is exactly what people with PCSK1 variants need [</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><a href="https://pubmed.ncbi.nlm.nih.gov/19817705/"><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 </span><a href="https://selfhacked.com/blog/ways-to-lose-weight-fast/"><span style="font-weight: 400;">weight loss</span></a><span style="font-weight: 400;">, metabolism, and satiety (fullness) [</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="font-weight: 400;">Great protein sources include [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/26797090"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.nutrition.gov/topics/whats-food/proteins"><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;">Eggs</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Meat &amp; fish</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Legumes</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Dairy</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Nuts and seeds</span></li> </ul> <h4><strong>Spicy Food</strong></h4> <p><a href="http://selfhacked.com/blog/capsaicin/"><span style="font-weight: 400;">Capsaicin</span></a><span style="font-weight: 400;"> may improve leptin resistance and stimulate POMC release [</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><a href="https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.2006188"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Spicy foods containing capsaicin, 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="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Increase protein intake and eat spicy food to lessen the impact of your variant and improve weight loss.</span></p> <h3><strong>Supplements</strong></h3> <h4><strong>Green Coffee Extract</strong></h4> <p><a href="https://www.selfhacked.com/blog/chlorogenic-acid/"><span style="font-weight: 400;">Chlorogenic acid</span></a><span style="font-weight: 400;">, the active compound in green coffee extract, increased POMC levels in mice. Caffeine from green coffee may also stimulate the leptin-melanocortin pathway&nbsp; [</span><a href="https://www.tandfonline.com/doi/full/10.1080/19768354.2010.528192"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.sciencedirect.com/science/article/abs/pii/S1756464618302470"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In 12 healthy volunteers, chlorogenic acid-enriched coffee increased weight loss by reducing sugar absorption. In another small trial, chlorogenic acid from coffee increased fat burning during sleep [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18035001"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/28412986"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Both green coffee extract and a natural supplement with chlorogenic acid reduced body weight and blood lipids in two clinical trials of 121 people with metabolic syndrome [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29307310"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/25632052"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Similarly, chlorogenic acid reduced BMI and WC in 30 people with prediabetes (impaired glucose tolerance) [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/29261010"><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;">Chlorogenic acid and caffeine from green coffee extract may activate the leptin-melanocortin pathway and slightly improve weight loss.</span></p> <h4><strong>Green Tea Extract</strong></h4> <p><span style="font-weight: 400;">A combination of EGCG and </span><a href="https://selfhacked.com/blog/caffeine-benefits/"><span style="font-weight: 400;">caffeine</span></a><span style="font-weight: 400;">, both found in </span><a href="https://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">green tea</span></a><span style="font-weight: 400;">, increased POMC expression in the hypothalamus in mice [</span><a href="https://www.sciencedirect.com/science/article/abs/pii/S1756464618302470"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a review of 11 studies, green tea extract or EGCG slightly improved weight loss and maintenance. However, a Cochrane database review of 14 studies regarded the weight changes as nonsignificant in most studies, so the evidence is inconclusive [</span><a href="https://pubmed.ncbi.nlm.nih.gov/19597519/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23235664/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The majority of weight loss trials used special extracts with higher concentrations of active ingredients (catechins and caffeine), compared with regular tea. Hence, it may be necessary to take green tea extract for beneficial effects [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4025876/"><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;">Green tea extract rich in EGCG and caffeine may enhance fat burning and weight loss, but the evidence is inconclusive.</span></p>
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219 | content_learn_more_6900898855823863_text == Based on the variants we looked at, your PCSK1 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. Exercise regularly, increase protein intake, and follow other gene-based tips to maintain a healthy weight. Keep reading to find out more.
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rsIDs = rs6232,rs6235,rs6234
rsStatus = rs6232,PCSK1,chr5,96416081,T,C,,,40,0,Normal
rsStatus = rs6235,PCSK1,chr5,96393194,C,G,,,18,8,HET
rsStatus = rs6234,PCSK1,chr5,96393270,G,C,,,20,17,HET
