Does This Gene Influence Your Risk of Obesity and Diabetes? (UCP2)

Low-Calorie Mediterranean Diet

The Mediterranean diet is rich in fruits and vegetables, and includes regional foods such as olive oil, nuts, whole grains, fish, and wine. It contains more fiber and polyunsaturated fatty acids (‘healthy fat’) than a standard Western-style diet.

The ‘T’ variant of rs659366 reduced the risk of obesity in Indonesian adolescents eating high-fat diets. In French adolescents, this variant altered energy metabolism to obtain more energy from carbohydrates and less from fats [R, R].

The ‘A’ variant of rs660339 was associated with reduced weight loss from calorie restriction in Korean women. Conversely, Korean women on a very-low-calorie diet and obese Taiwanese taking an appetite-suppressant drug lost more weight if they carried the ‘T’ variant of rs659366 [R, R, R].

A study on Brazilian women found that the UCP2 protein contributed to the effectiveness of a low-calorie diet [R].

Several studies in mice and rats found that UCP2 expression is increased in fatty tissue as a response to high-fat Western diets [R, R, R, R].

The Mediterranean diet is an effective alternative to low-fat and low-carbohydrate diets in weight-loss interventions. Because it improves both blood fat levels and sugar control, this diet also helps prevent heart disease and metabolic disorders such as type 2 diabetes and metabolic syndrome [R, R, R, R].

This diet is most effective when calorie-restricted. Eating low-calorie diets helps reduce fat buildup and food cravings while increasing adiponectin levels and fat burning [R, R].

Coffee

In an Indonesian study, carriers of the ‘T’ variant at rs659366 lost more weight and body fat in response to high coffee intake [R].

Caffeine increased UCP2 expression in the brown fat and muscles of obese mice, as well as in cultured cells [R, R].

Caffeine is a well-known metabolic booster. In 12 clinical trials on 135 people, caffeine (100-600 mg/day) increased energy use and fat burning. Paradoxically, the effects were more pronounced in lean than in overweight people. Caffeine also helped maintain weight loss in 2 long-term studies on 2,500 people [R, R, R, R, R, R, R, R, R, R, R].

Chilli Peppers (Capsaicin)

In a clinical trial on overweight and obese people, a 12-week treatment with non-spicy capsaicin analogs isolated from chilli peppers caused abdominal fat loss. Carrying the ‘T’ variant at rs659366 further enhanced their effects [R].

Both capsaicin and a non-spicy analog (capsiate) increased UCP2 expression in fatty tissues and reduced fat buildup in animal and cell-based studies [R, R, R].

Capsaicin activates receptors (TRPV1) that may speed up the metabolism, increase energy expenditure, and reduce appetite by activating key proteins of energy metabolism [R, R, R, R].

When ingested orally with green tea, capsaicin reduced appetite and food intake in human studies [R, R].

If you like spicy food, you’re in luck: capsaicin is found in chili peppers and is responsible for their spicy flavor. The spicier the pepper, the more capsaicin it contains [R, R].

Fish & Seafood

In mice and rats, dietary fish oil increased UCP2 expression in the muscles and fatty tissues, resulting in an increased fat burning [R, R, R, R, R].

Fish is hypothesized to reduce leptin; higher leptin is associated with obesity. In young, overweight men, the inclusion of 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].

Eating a low-calorie Mediterranean diet, as well as increasing the intake of coffee, chilli peppers, and fish or seafood, help reduce weight. Some UCP2 variants may enhance or reduce the effects of these dietary interventions.

Exercise

The ‘A’ variant of rs660339 has been associated with increased endurance in Polish, Danish, Russian, and Indonesian studies. Unfortunately, this seems due to reduced energy expenditure and fat burning [R, R, R, R, R].

The ‘T’ variant of rs659366 was also associated with increased energy efficiency in response to endurance training in a British study. This means that endurance training doesn’t help people with the ‘T’ variant lose as much weight [R].

In mice and rats, endurance training reduced UCP2 expression in the muscles and increased energy efficiency. Conversely, exhaustive training increased UCP2 levels in white fat and muscles [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

Cold exposure increased UCP2 expression in animal studies, especially if the animals were young and overweight (but not diabetic) [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].

High-intensity exercise and cold exposure help reduce weight by increasing energy expenditure and UCP2 levels. Conversely, endurance training increases energy efficiency and reduces UCP2 expression.

Green Tea

Both green tea and its active compound epigallocatechin gallate (EGCG) increased UCP2 expression in both animals fed high-fat diets and fatty cells. In the animal studies, this resulted in reduced fat levels in fatty tissues, blood, and liver [R, R, R, R, R, R].

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 a high-fat and -sugar diet, supplementation with calcium reduced weight gain and increased the expression of the UCP2 and UCP3 genes [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

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].

In animal studies, including CLA in the diet prevented obesity and increased UCP2 expression in fatty tissues (both white and brown), muscles, and mammary glands [R, R, R, R, 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].

Berberine

Berberine is an alkaloid with potent metabolic effects. People use berberine as a supplement to support weight control and glucose metabolism.

In animal studies, dietary berberine increased the expression of UCP2 and other genes involved in energy metabolism [R, R, R].

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 [R, R].

According to a 2020 review of human and animal studies, berberine might contribute to weight loss by improving gut microbiota and glucose and fat metabolism [R].

Preliminary research in animals suggests that supplementing with EGCG, calcium, CLA, and berberine may help lose weight, in part by increasing UCP2 levels.