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NPC1

Could Your Cells Be Storing Fat Incorrectly? (NPC1)

Written by Jasmine Foster, BSc, BEd on July 13th, 2020

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.

What is NPC1?

NPC1 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 [R].

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 NPC1. 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 [R, R].

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 [R].

Some variants in NPC1 have more recently been associated with obesity and weight gain without the neurological decay and other symptoms of NPD type C1 [R].

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.

Does NPC1 Cause Weight Gain?

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 [R].

Malfunctioning NPC1 may also cause problems with steroid hormone production and activity, which may cause various metabolic disruptions in turn. Steroid hormones (mainly cortisol and sex hormones) are produced from cholesterol; mutations in NPC1 may prevent adequate amounts of these hormones from being produced [R].

Steroid hormones are well-known to affect appetite and weight gain. In women, for example, high levels of estrogen are associated with weight loss and low appetite, while the opposite is true for low estrogen. Similarly, low testosterone may cause a buildup of body fat and other metabolic disruptions [R].

Whatever the mechanism, mutations in the NPC1 gene are believed to have a dramatic effect on weight [R].

Problems in the NPC1 transport system may cause disruptions in cholesterol transport and steroid hormone production, both of which can cause weight gain.

NPC1 Variants & Obesity

Some research suggests that two copies of mutated, non-functional NPC1 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 [R, R, R].

If you have risk alleles at rs120074135 or rs80358259 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.

Not all NPC1 mutations result in a non-functional protein, however, and there is evidence that less dramatic variants could account for surprisingly large differences in weight [R, R].

At least three such variants have been the subject of obesity research: rs1808579-C, rs1805081-T, and rs1805082-T [R, R, R, R].

A single variant allele in NPC1 may increase the odds of developing obesity, and mutations in both alleles can cause Niemann-Pick disease.

Your NPC1 Results for Weight Gain

SNP Table

variant	genotype	frequency	risk allele
rs1808579
rs1805081
rs1805082

SNP Summary and Table

NPC1 rs1808579

‘T’ = Associated with lower BMI and hip circumference
‘C’ = Associated with obesity, increased BMI, and increased hip circumference

NPC1 rs1805081

‘T’ = Associated with obesity (in both childhood and adulthood), increased BMI, metabolic disorders, and coronary heart disease
‘C’ = Possibly protective against obesity and metabolic disruption

NPC1 rs1805082

‘T’ = Associated with obesity and increased BMI
‘C’ = Possibly protective against obesity

NPC1 rs120074135

‘C’ = Not associated with obesity or metabolic disease
‘T’ = Associated with obesity (heterozygous CT) and Niemann-Pick disease (homozygous TT)

NPC1 rs80358259

‘A’ = Not associated with obesity or metabolic disease
‘G’ = Associated with obesity (heterozygous AG) and Niemann-Pick disease (homozygous GG)

Recommendations

Lifestyle

Exercise

One study found that physical exercise 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 [R].

People with Niemann-Pick disease generally undergo physical therapy focused on maintaining mobility and balance [R].

High-intensity exercise is probably the best strategy to lose weight. In addition to promoting fat burning, the increased norepinephrine production may suppress food intake according to a study in rats [R].

Being active burns calories and jump-starts metabolism. Some studies suggest it also increases BDNF, which supports mental health and might cause us to eat less [R].

Exercise also increases endorphins, which activates mu-opioid receptors and also suppresses appetite [R].

Aerobic exercise (like walking, running, swimming, etc) has also been shown to cause major reductions in belly fat in multiple studies [R, R].

Although the reason is not fully understood, yoga can be a useful tool for weight loss too [R, R, R].

Physical exercise may help counteract the detrimental effects of variant NPC1 and is strongly recommended as part of every weight loss program.

Diet

Reduce Dietary Fats

NPC1 mutations cause problems with fat metabolism, transport, and storage; some researchers believe that people with NPC1 mutations may gain more weight from dietary fat [R].

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 NPC1 variants, it may be worth reducing dietary intake of fats [R, R].

Increase Dietary Fiber

The dysfunction in nerve cells affected by NPC1 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 NPC1 mutations may benefit from an increase in dietary fiber, which adds bulk to the feces and improves stool consistency [R].

Fiber, both from foods and supplements, is also known to increase satiety after a meal and decreases subsequent hunger. Studies suggest that an additional 14 g of fiber per day is associated with a 10% lower energy intake and weight loss [R].

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 [R].

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 [R]!

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 butyrate, which has weight loss effects in animals [R, R, R, R].

Due to NPC1’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.

Jasmine Foster

BSc, BEd

Jasmine received her BS from McGill University and her BEd from Vancouver Island University.

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.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

More nutrition blogs

The Role of Genes in Choline Deficiency (PEMT) A Surprising Player in Obesity and Diabetes (PEMT) A Heat-Generating Gene Linked to Weight Gain (UCP1) Can Our Genes Make Us Fat? (FTO) Can This Gene Affect Vitamin B12 Levels? (FUT2) The Role Of Amino Acids In Diet, Obesity, & Diabetes (PPM1K) How A Fat Metabolism Gene Affects Nutrition and Cognition (FADS2) The Link Between Diabetes and High-Carb Foods (TCF7L2) How An Insulin Gene Influences Diet and Blood Sugar (GIPR) Can This Fat Metabolism Gene Influence Nutrition and Cholesterol? (FADS1)

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What is NPC1? Does NPC1 Cause Weight Gain? NPC1 Variants & Obesity Your NPC1 Results for Weight Gain

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Could Your Cells Be Storing Fat Incorrectly? (NPC1)

What is NPC1?

Does NPC1 Cause Weight Gain?

NPC1 Variants & Obesity

Your NPC1 Results for Weight Gain

SNP Table

SNP Summary and Table

Recommendations

Lifestyle

Diet

Disclaimer

More nutrition blogs

Content

Unlock Personalized Results And So Much More!

Essential Bundle

Essential

Bundle

Ultimate Bundle

Limited Time Offer 25% Off

Individual DNA Reports

Methylation Pathway - MTHFR Test

Histamine Intolerance DNA Pathway Report

Gut Health, Digestion & IBS DNA Report

Autoimmune Disease Risk & Prevention DNA Report

See all reports

Policies

About

Navigation

Health reports