Is This Gene Linked to Severe Obesity (INSIG2)?

Exercise

In a trial on American and Irish Caucasian men, carriers of the ‘C’ variant lost less body fat from resistance training [R].

Similarly, obese children and adolescents with the ‘C’ variant lost less weight from an intervention combining exercise and dietary education in two German studies [R, R].

A Danish study failed to associate this variant with obesity, but found that carriers gained more weight during periods of physical inactivity [R].

However, this variant increased the positive effects of a lifestyle intervention in a multi-ethnic American study and carriers of the ‘G’ allele re-gained more intramuscular fat in the arm one year after stopping a physical training [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].

Moderate Sun Exposure

In pregnant rats, supplementation with vitamin D reduced weight and the amount of fat stored in fat cells, while increasing INSIG2 expression in fatty tissues [R].

In one study, intense light exposure, particularly in the morning, was associated with a lower BMI independent of sleep duration and timing. In another trial, exposure to at least 45 minutes of morning light for 3 weeks in obese women resulted in reduced body fat and appetite [R, R].

Both UV radiation and vitamin D (whose production is stimulated by UV) are suspected to help prevent obesity [R, R].

Exercise helps reduce weight, but an INSIG2 variant associated with obesity may attenuate its positive effects. Vitamin D produced in response to sun exposure seems to prevent obesity and increase INSIG2 expression in fatty tissues.

Low-Saturated Fat Diets

In a clinical trial on New Zealander bipolar patients who gained weight from the medication, a low-fat dietary intervention was less effective in those carrying the ‘C’ variant. However, this effect could be reversed by supplementing with L-carnitine [R].

In another trial on a Samoan population, people with two copies of the minor C variant at another INSIG2 polymorphism (rs9308762) had higher BMI and blood triglyceride levels in response to a Western-style, fat-rich diet [R].

A high-fat diet increased INSIG2 expression in the fatty tissues of lean pigs, possibly indicating increased fat production in these tissues [R].

Several meta-analyses have associated low-fat diets with significant and sustained weight loss, as well as with reduced weight gain. Omega 3’s and MUFAs from olive oil are very healthy, so it would be wisest to cut down on saturated fat [R, R, R].

Fish/Seafood

In rats, omega-3 deficiency greatly reduced INSIG2 expression in the liver while high-fat diets increased it. In both cases, supplementation with fish oil normalized INSIG2 levels [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].

Cutting down on saturated fats helps weight loss, although INSIG2 variants may alter its effects. Omega 3-rich fish and seafood also helps lose weight and may help normalize INSIG2 levels.

Green Tea

In mice fed a high-fat diet, green tea prevented the development of NAFLD by increasing the expression of INSIG2 and other genes involved in fat metabolism [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 7.3 lbs and burned 183 more calories per day (on average) after 3 months [R, R].

Supplementing with green tea’s epigallocatechin gallate helps weight loss and may increase INSIG2 expression.