Does This Gene Influence Your Risk of Obesity and Diabetes? (UCP3)

High-Protein, Low-Carbohydrate Diets

In a Spanish study, weight loss and blood insulin and leptin levels were similar after either a low-fat or a low-carbohydrate diet in obese carriers of both rs1800849 variants [R]. 

However, three more recent studies by the same group found that obese carriers of the ‘G’ allele experienced a higher reduction in weight, fat mass, waist circumference, and blood fats after adopting a high-protein/low-carbohydrate diet, a conventional low-calorie diet, or a low-calorie diet rich in monounsaturated fatty acids [R, R, R].

Eating a high-fat diet is associated with lower UPC3 expression in the muscles of rats, suggesting that dietary fats may suppress the beneficial effect of the ‘A’ variant on obesity prevention [R].

Some research suggests that getting more calories from proteins (as opposed to either carbohydrates or fat) may support weight loss, metabolism, and satiety. High-protein diets appeared to increase fat burning and weight loss and reduce appetite in a handful of human studies [R, R, R].

In a clinical trial on 119 overweight people, a low-carbohydrate ketogenic diet was as effective as a low-fat diet for weight loss but had the advantages that it reduced appetite and negative affect. A meta-analysis of 13 studies and over 1,500 people concluded that low-carbohydrate ketogenic diets are more effective than low-fat diets for losing weight [R, R].

Fish & Seafood

In mice and rats, dietary fish oil increased UCP3 expression in the muscles and reduced obesity and insulin resistance [R, R, R, R, R].

Fish is hypothesized to reduce leptin; higher leptin is associated with obesity. In young, overweight men, the inclusion of either lean or fatty fish or fish oil as part of an energy-restricted diet resulted in approximately 1 kg more weight loss after 4 weeks compared to a similar diet without seafood or a supplement [R, R].

Fish oil’s anti-inflammatory effects have the ability to indirectly aid in fat metabolism in people with high inflammation or metabolic syndrome. It can increase the secretion of adiponectin, which is responsible for breaking down fats [R, R].

In a large meta-analysis of 21 clinical trials, fish oil in combination with lifestyle changes significantly reduced waist-to-hip ratio although it failed to improve weight loss [R].

Intermittent Fasting

In a small trial on 14 people, eating a very low-calorie diet for 5 days caused a ~2-fold increased expression of UCP3 [R].

In mice and rats, repeated cycles of fasting and refeeding increased UCP3 expression in the muscles and prevented high-fat-induced obesity [R, R].

Intermittent fasting describes any diet in which a person eats their required caloric intake during predetermined periods of time and fasts during the remaining time. Some people choose to eat only during specific times of day (for example, between 10 AM and 6 PM), while others choose to fast for one or two entire days per week.

Fasting every other day for 12 weeks caused 32 people to lose an average of 12 pounds more than those who followed a daily program of calorie restriction. These people ate 25% of their calories every other day [R].

In a clinical trial on 52 women, caloric intake after 8:00 PM increased the risk of obesity, independent of sleep timing and duration [R].

Time-restricted feeding, a strategy in which a person only eats during a specific window of time each day, has also produced good results for weight loss. However, time-restricted feeding was not as effective as other forms of intermittent fasting, according to a meta-analysis of the practice [R, R, R].

Dark Chocolate

Cocoa enhanced energy expenditure and increased UCP3 levels in mice and rats [R, R, R].

Cocoa contains polyphenols that are believed to promote weight gain, though clinical studies are few and far between. In one study, daily consumption of 49 grams of dark chocolate reduced snacking, suggesting that cocoa might decrease appetite or cravings [R].

In a study in rats, those fed cocoa had less fat production in the belly. In mice, cocoa consumption reduced weight gain and fat uptake in the gut. Cocoa also reduced inflammation associated with obesity and improved insulin resistance [R, R].

Eating a diet high in proteins and low in fats and carbohydrates, practicing intermittent fasting, and including more fish and dark chocolate in the diet may help lose weight and increase UCP3 activity.

Exercise

A Colombian study found an association of the major ‘G’ variant of rs1800849 with obesity only in people who didn’t exercise much. Similarly, the ‘A’ variant only prevented obesity in Spanish people with a high level of physical activity [R, R].

In contrast, a Danish study concluded that the rs1800849 genotype had no influence on weight loss due to physical exercise. This discrepancy may be due to the effects on the different types of exercise (acute versus endurance) on UCP3 expression [R, R, R, R, R].

High-intensity exercise is probably the best strategy to lose weight. In addition to promoting fat and calorie burning, it may increase the levels of chemicals that support mental health and suppress appetite such as the neurotransmitters norepinephrine and endorphins, and the neurotrophin BDNF [R, R, R].

Aerobic exercise (like walking, running, swimming, etc) has also been shown to cause major reductions in belly fat in multiple studies. Although the reason is not fully understood, yoga can be a useful tool for weight loss too [R, R, R, R, R].

Cold Exposure

In animal studies, acute cold exposure increased UCP3 expression in the muscles and brown fat. However, prolonged exposure suppressed this effect [R, R, R, R, R, R, R, R].

Cold increases metabolism and energy expenditure as the body has to adapt and produce more heat. In a clinical trial of 50 healthy men, those exposed to a cool environment overnight for a month had a 42% increase in brown fat with a corresponding 10% increase in metabolism [R].

Exercise and cold exposure help reduce weight by increasing energy expenditure. Physical exercise influences the effects of UCP3 variants on obesity. In turn, acute cold exposure increases UCP3 activity but may have the opposite effect after longer periods.

Green Tea

In a small trial on 11 obese women, supplementation with EGCG increased the expression of UCP3 and other genes involved in energy and fat metabolism. However, it didn’t promote weight loss [R].

In mice, EGCG had similar effects on UCP3 expression and reduced dietary fat uptake, likely helping prevent weight gain [R].

Green tea’s active compound epigallocatechin gallate (EGCG) caused between 0.2 and 3.5 kg of weight loss in limited human studies. Green tea, meanwhile, is hypothesized to make us burn more calories, even at rest. In most studies, this amounts to a modest 3-4% increase in energy, though some studies have shown an increase as high as 8%. For a 2,000 calorie diet, 3-4% amounts to an additional 60-80 calories per day [R, R, R, R].

In one study of 60 obese individuals, the group taking green tea extract lost 7.3lbs and burned 183 more calories per day (on average) after 3 months [R, R].

Calcium

In mice fed high-fat diets, calcium supplementation increased UCP3 levels and prevented weight gain [R, R, R].

A clinical trial of 53 people found that calcium (600 mg/day) and vitamin D (125 IU/day) enhanced weight loss when combined with a restricted diet [R].

In another study of 32 obese adults, increased dietary calcium promoted weight loss and fat loss, primarily in the abdomen. Participants who ate a low-calcium diet experienced about 19% of their fat loss from the abdominal region, while those who ate a high-calcium diet experienced about 50% [R].

However, a recent review of 41 studies concluded that calcium supplements don’t increase total weight loss [R].

Conjugated Linoleic Acids

In mice and hamsters, dietary CLA increased UCP3 levels in the muscles [R, R, R].

Conjugated linoleic acids (CLA) are poly-unsaturated fatty acids. Studies have shown that CLAs decrease lipid storage by increasing the rate of fat breakdown in fat tissue [R].

A clinical trial on overweight Chinese subjects found that CLA supplementation over a 12-week period reduced body weight, BMI, total fat mass, fat percentage, waist to hip ratio, and subcutaneous fat mass [R].

It should be noted, though, that CLA supplementation did not prevent weight or fat regain after initial weight loss in a similar study in obese people [R, R].

Resveratrol

Both resveratrol and a compound combining four molecules of this polyphenol (vaticanol C) increased UCP3 expression in the muscles of obese mice and rats [R, R].

In mice fed a high-fat diet, resveratrol reduced oxidative stress and prevented the death of protective immune cells called Tregs [R].

Resveratrol stopped fat cells from making new fats and triggered their death, in cell-based studies. It accomplishes this by turning off genes that cause weight gain (such as PPAR gamma) and blocking fat-creating enzymes (fatty acid synthase, lipoprotein lipase, and hormone-sensitive lipase) while activating genes that enhance energy use and mitochondrial health (SIRT3, UCP1) [R, R].

Supplementing with EGCG, calcium, CLA, and resveratrol may help lose weight, in part by increasing UCP3 levels.