244 | id == 244
244 | category_id == 18
244 | category_order == 15
244 | category_name == Weight
244 | category_color == #C47AC0
244 | slug == NPC1-weight
244 | title == Could Your Cells Be Storing Fat Incorrectly? (NPC1)
244 | meta_description == NPC1 encodes a fat transport protein that has been associated with weight gain, obesity & dangerous metabolic disorders.
244 | summary == <p><strong>NPC1 encodes a fat transport protein that has been associated with weight gain, obesity, and dangerous metabolic disorders. Which variants have the greatest effect? Read on to find out.</strong></p>
244 | overall_score_text == Weight Score (based on NPC1)
244 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/NPC1--Weight.jpg
244 | author_id == 1
244 | author_name == Jasmine Foster
244 | author_title == BSc, BEd
244 | author_order == 36
244 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/Jasmine.jpg
244 | author_intro == <p><strong>Jasmine received her BS from McGill University and her BEd from Vancouver Island University.</strong></p>    <p>Jasmine loves helping people understand their brains and bodies, a passion that grew out of her dual background in biology and education. From the chem lab to the classroom, everyone has the right to learn and make informed decisions about their health.</p>
244 | reviewer == None
244 | medical_reviewer_id == 11
244 | medical_reviewer_name == Puya Yazdi
244 | medical_reviewer_title == MD
244 | publish_date == 2020
244 | publish_date == 7
244 | publish_date == 13
244 | avg_rating == 5.0
244 | tags_id == 152
244 | tags_name == Cholesterol
244 | tags_id == 305
244 | tags_name == Fat burning
244 | tags_id == 543
244 | tags_name == Niemann-Pick Disease
244 | tags_id == 544
244 | tags_name == NPC1 Gene
244 | tags_id == 115
244 | tags_name == Weight Gain
244 | tags_id == 184
244 | tags_name == Weight Loss
244 | permissions_favorite == False
244 | permissions_rate == False
244 | 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><span style="font-weight: 400;">What is NPC1?</span></h2> <p><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> encodes a cholesterol transporter protein that moves cholesterol into, out of, and around inside cells. Beyond that, its exact function is a bit of a mystery; however, it is present in lysosomes and endosomes, parts of the cell responsible for recycling and disposing of waste materials [</span><a href="https://ghr.nlm.nih.gov/gene/NPC1"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This gene is best-known for its association with Niemann-Pick Disease (NPD) type C1. If a person has a mutation that produces a non-functional version of </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;">. As a result, cholesterol and other fats do not move around properly, leading to fatty buildup inside cells. Children with Niemann-Pick Disease quickly develop movement problems, neurological and intellectual impairment, liver disease, and lung disease [</span><a href="https://ghr.nlm.nih.gov/gene/NPC1"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://ghr.nlm.nih.gov/condition/niemann-pick-disease"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">There is no cure for Niemann-Pick Disease. Children with NPD type C1 may survive into adulthood (unlike those with type A or B), but neurological disorders eventually lead to problems eating, swallowing, and breathing [</span><a href="https://ghr.nlm.nih.gov/condition/niemann-pick-disease"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Some variants in </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> have more recently been associated with obesity and weight gain without the neurological decay and other symptoms of NPD type C1 [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888214/"><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;">NPC1 encodes a cholesterol transporter which, if mutated, can cause Niemann-Pick disease type C1. Less dramatic variants have been associated with weight gain and obesity.</span></p> <h2><span style="font-weight: 400;">Does NPC1 Cause Weight Gain?</span></h2> <p><span style="font-weight: 400;">When it is working correctly, NPC1 (alongside the closely related NPC2) is part of a system that transports cholesterol and other fats. If this transport system is interrupted, it may result in fats building up inside cells [</span><a href="https://ghr.nlm.nih.gov/gene/NPC1"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Malfunctioning NPC1 may also cause problems with steroid hormone production and activity, which may cause various metabolic disruptions in turn. Steroid hormones (mainly </span><a href="https://selfhacked.com/blog/need-know-cortisol-health-effects/"><span style="font-weight: 400;">cortisol</span></a><span style="font-weight: 400;"> and sex hormones) are produced from cholesterol; mutations in </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> may prevent adequate amounts of these hormones from being produced [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888214/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Steroid hormones are well-known to affect appetite and weight gain. In women, for example, high levels of </span><a href="https://selfhacked.com/blog/estradiol/"><span style="font-weight: 400;">estrogen</span></a><span style="font-weight: 400;"> are associated with weight loss and low appetite, while the opposite is true for low estrogen. Similarly, low </span><a href="https://selfhacked.com/blog/testosterone-will-add/"><span style="font-weight: 400;">testosterone</span></a><span style="font-weight: 400;"> may cause a buildup of body fat and other metabolic disruptions [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888214/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Whatever the mechanism, mutations in the </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> gene are believed to have a dramatic effect on weight [</span><a href="https://pubmed.ncbi.nlm.nih.gov/19151714/"><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;">Problems in the NPC1 transport system may cause disruptions in cholesterol transport and steroid hormone production, both of which can cause weight gain.</span></p> <h2><span style="font-weight: 400;">NPC1 Variants &amp; Obesity</span></h2> <p><span style="font-weight: 400;">Some research suggests that two copies of mutated, non-functional </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> are required to produce Niemann-Pick Disease. People with only one copy of the non-functional protein may have less severe metabolic disruption in the form of obesity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888214/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1288284/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2276376/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">If you have risk alleles at </span><a href="../../../snp/rs120074135/"><span style="font-weight: 400;">rs120074135</span></a><span style="font-weight: 400;"> or </span><a href="../../../snp/rs80358259/"><span style="font-weight: 400;">rs80358259</span></a><span style="font-weight: 400;"> in your genetic results, we recommend alerting your doctor, who may wish to order more specific tests, especially if you have or are planning to have children.</span></p> <p><span style="font-weight: 400;">Not all </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> mutations result in a non-functional protein, however, and there is evidence that less dramatic variants could account for surprisingly large differences in weight [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888214/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19151714/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">At least three such variants have been the subject of obesity research: </span><a href="../../../snp/rs1808579/"><span style="font-weight: 400;">rs1808579</span></a><span style="font-weight: 400;">-C, </span><a href="../../../snp/rs1805081/"><span style="font-weight: 400;">rs1805081</span></a><span style="font-weight: 400;">-C, and </span><a href="../../../snp/rs1805082/"><span style="font-weight: 400;">rs1805082</span></a><span style="font-weight: 400;">-T. Each &lsquo;C&rsquo; allele of rs1805081 may increase the odds of childhood obesity by 12-57% and of adulthood obesity by 39-46% [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382211/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247512/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5888214/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19151714/"><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;">A single variant allele in NPC1 may increase the odds of developing obesity, and mutations in both alleles can cause Niemann-Pick disease.</span></p> <h2><span style="font-weight: 400;">Your NPC1 Results for Weight Gain</span></h2> <p>*6749828932504132*</p> <h3><span style="font-weight: 400;">SNP Summary and Table</span></h3> <p><strong>NPC1 rs1808579</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with lower BMI and hip circumference</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Associated with obesity, increased BMI, and increased hip circumference</span></li> </ul> <p><strong>NPC1 rs1805081</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with obesity (in both childhood and adulthood), increased BMI, metabolic disorders, and coronary heart disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Possibly protective against obesity and metabolic disruption</span></li> </ul> <p><strong>NPC1 rs1805082</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with obesity and increased BMI</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Possibly protective against obesity</span></li> </ul> <p><strong>NPC1 rs120074135</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Not associated with obesity or metabolic disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with obesity (heterozygous CT) and Niemann-Pick disease (homozygous TT)</span></li> </ul> <p><strong>NPC1 rs80358259</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Not associated with obesity or metabolic disease</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Associated with obesity (heterozygous AG) and Niemann-Pick disease (homozygous GG)</span></li> </ul> <p>*1516369920279898*</p> <h2><span style="font-weight: 400;">Recommendations for Reducing Fat Buildup</span></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>*6192368190916121*</p> <h3><span style="font-weight: 400;">Lifestyle</span></h3> <h4><span style="font-weight: 400;">Exercise</span></h4> <p><span style="font-weight: 400;">One study found that physical </span><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;"> improved the function of nerve and muscle cells in mice with NPC1 mutations. The authors suggested that the improved function could be caused by improved cholesterol clearance from the cells [</span><a href="https://pubmed.ncbi.nlm.nih.gov/31850859/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">People with Niemann-Pick disease generally undergo physical therapy focused on maintaining mobility and balance [</span><a href="https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0785-7"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">High-intensity exercise 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;">. In addition to promoting fat burning, the increased </span><a href="https://selfhacked.com/blog/norepinephrine-stress-hormone/"><span style="font-weight: 400;">norepinephrine</span></a><span style="font-weight: 400;"> production may suppress food intake according to a study in rats [</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></p> <p><span style="font-weight: 400;">Being active burns calories and jump-starts metabolism. Some studies suggest it also </span><a href="https://selfhacked.com/blog/a-comprehensive-list-of-natural-ways-to-increase-bdnf/"><span style="font-weight: 400;">increases </span></a><a href="../../article/boost-plasticity-with-the-bdnf-gene-50"><span style="font-weight: 400;">BDNF</span></a><span style="font-weight: 400;">, which supports mental health and might cause us to eat less [</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></p> <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;">also increases </span><a href="https://selfhacked.com/blog/endorphins/"><span style="font-weight: 400;">endorphins</span></a><span style="font-weight: 400;">, which activates mu-opioid receptors and also suppresses appetite [</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 (like walking, running, swimming, etc) has also been shown to cause major 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="font-weight: 400;">Although the reason is not fully understood, </span><a href="https://selfhacked.com/blog/health-benefits-yoga/"><span style="font-weight: 400;">yoga</span></a><span style="font-weight: 400;"> can be a useful tool for </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;"> too [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995338/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098025/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">,</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198375/"><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;"><span style="font-weight: 400;">Physical exercise may help counteract the detrimental effects of variant </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> and is strongly recommended as part of every weight loss program.</span></span></p> <h3><span style="font-weight: 400;">Diet</span></h3> <h4><span style="font-weight: 400;">Reduce Dietary Fats</span></h4> <p><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> mutations cause problems with fat metabolism, transport, and storage; some researchers believe that people with </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> mutations may gain more weight from dietary fat [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5582887/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Low-fat diets have become controversial as a means for weight loss, especially as we understand more about the relationship between simple carbs and body fat gain. However, in specific cases such as </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> variants, it may be worth reducing dietary intake of fats [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893678/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4428290/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <h4><span style="font-weight: 400;">Increase Dietary Fiber</span></h4> <p><span style="font-weight: 400;">The dysfunction in nerve cells affected by </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> mutations may lead to disturbances in gut movement and increases in the amount of time it takes for food to pass through the intestine. People with </span><em><span style="font-weight: 400;">NPC1</span></em><span style="font-weight: 400;"> mutations may benefit from an increase in dietary fiber, which adds bulk to the feces and improves stool consistency [</span><a href="https://ojrd.biomedcentral.com/articles/10.1186/s13023-018-0785-7"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Fiber, both from foods and supplements, is also known to increase satiety after a meal and decreases subsequent</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;">. Studies suggest that an additional 14 g of fiber per day is associated with a 10% lower energy intake and weight loss [</span><a href="https://pubmed.ncbi.nlm.nih.gov/11396693/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">How much is 14g? To put it into perspective, in the US, the average fiber intake is around 15 g/day which is only half of the recommended amount [</span><a href="https://pubmed.ncbi.nlm.nih.gov/11396693/"><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 62 trials with over 3.8k people, soluble fiber modestly but significantly improved body weight and decreased waist circumference even without calorie restriction [</span><a href="https://pubmed.ncbi.nlm.nih.gov/31897475/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">]!</span></p> <p><span style="font-weight: 400;">Vegetables are rich in soluble fiber, which has been shown to cause weight loss in some studies. Fiber gets broken down by bacteria in the digestive tract to produce </span><a href="http://selfhacked.com/blog/health-benefits-butyrate-derivatives-sodium-butyrate-phenylbutyrate-trybutyrine-butyric-acid-butyrate-prodrugs-butyrate-producing-bacteria/"><span style="font-weight: 400;">butyrate</span></a><span style="font-weight: 400;">, which has weight loss effects in animals [</span><a href="https://www.sciencedirect.com/science/article/pii/S019566639790091X"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/18031592"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/21810257"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699871/"><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;">Due to NPC1&rsquo;s effects on fat metabolism and gut transit, people with variant alleles may benefit more than the general population from a low fat, high-fiber diet.</span></p>
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244 | content_learn_more_1516369920279898_text == Based on the variants we looked at, your NPC1 gene is moderately associated with weight gain and poor fat metabolism. However, this doesn't necessarily reflect your overall risk of obesity, just one gene related to it. Exercise, decreased dietary fats, and increased dietary fiber may help; read on to learn more.
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rsIDs = rs120074135,rs80358259,rs1805081,rs1805082,rs1808579
rsStatus = rs120074135,NPC1,chr18,23539418,C,T,,,37,0,Normal
rsStatus = rs80358259,NPC1,chr18,23536736,A,G,,,30,0,Normal
rsStatus = rs1805081,NPC1,chr18,23560468,T,C,,,33,0,Normal
rsStatus = rs1805082,NPC1,chr18,23540480,T,A,C,,33,0,Normal
rsStatus = rs1808579,NPC1,chr18,23524924,C,T,,,24,10,HET
