This Important Inflammation Gene May Cause Weight Gain (IL6)

If you see the red or yellow face at the top of this post, that means that you have genetic variants that confer lower IL-6 and possible weight gain. The gene-based recommendations for weight loss below can help increase beneficial IL-6 signalling from muscle cells to the hypothalamus.

Exercise

Exercise increases the production of beneficial IL-6 by muscle tissues. IL-6 produced by the muscles sends signals to the hypothalamus to increase leptin sensitivity and reduce appetite. People with lower expression of IL6 and IL6R may enjoy greater weight-loss benefits from exercise; those with the heterozygous ‘CG’ genotype at rs1800795 most of all [R, 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].

Exercise is the best strategy for weight loss for almost anyone, and the vast majority of doctors agree that you should stay physically fit, regardless of your genotype. However, people with low IL-6 may benefit more than others!

Physical exercise is well-known to increase anti-inflammatory IL-6 in the hypothalamus, where it increases leptin sensitivity and reduces appetite. Exercise may be most beneficial for people with low-expression IL6 or IL6R variants.

Improved Sleep Schedule

IL-6 concentrations change dramatically over the course of a night’s sleep. Some researchers believe that sleep deprivation decreases IL-6, which may help explain why loss of sleep depresses the immune system and makes us more susceptible to infection [R].

Dysregulated sleep, with increased REM sleep and decreased slow-wave sleep, may increase inflammatory IL-6 and cause its own set of problems. To balance IL-6 (in either direction), it is important to get a full night’s sleep every night, going to bed and getting up at the same time each day if possible [R, R].

Research over the past few decades has recognized the importance of circadian biology in obesity. Scientists think that circadian biology may have a massive influence on energy balance and metabolism [R].

In lab settings, mice who ate at the wrong time (when it’s dark for humans) gained more weight, despite the absence of any significant differences in calorie intake or activity over the course of the experiment. The authors suspect that their metabolism shifted [R].

According to another theory, a disrupted circadian rhythm may be why shift workers seem to be at an increased risk of obesity [R].

IL-6 concentrations in the brain change dramatically over the course of a good night’s sleep. For both IL-6 balance and weight loss, a regular sleep schedule is essential.

If you see the green face at the top of this post, that means that you have genetic variants that confer higher than average IL-6, which may be associated with lower baseline weight, but a potential susceptibility to inflammation. If you are struggling to lose weight, you may wish to focus on strategies that have been found to both decrease IL-6 and improve weight loss outcomes.

Fish & Seafood

DHA, an omega-3 fatty acid found primarily in fish and seafood, has been found to decrease inflammatory IL-6. It may therefore be beneficial for those with high-expression IL6 and IL6R variants [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].

DHA from fish and seafood decreases inflammatory IL-6 and may be most beneficial for people with high-expression IL6 variants.

Fruits & Vegetables

Fruits and vegetables are rich in antioxidant polyphenols, many of which have been found to decrease inflammatory IL-6. These include apigenin, luteolin, quercetin, resveratrol, and fisetin, all of which are abundant in popular fruits and vegetables [R, R, R, R, 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].

Fruits are good, too. In a study of 91 obese individuals, eating half a fresh grapefruit before meals caused weight loss of 3.5 pounds (1.6 kg) over a period of 12 weeks [R].

Polyphenols from various fruits (including blueberries and apples) led to lower weight in animal studies as well [R, R].

Many polyphenols in fruits and vegetables have been found to decrease IL-6 and promote weight loss; vegetables rich in soluble fiber have improved weight loss outcomes as well. Fruits and vegetables may be especially important for people with high IL-6.

Olive Oil

Olive oil is anti-inflammatory and has been found to reduce IL-6 production [R].

In a review of 11 clinical studies, olive oil-enriched diet significantly reduced BMI and waist circumference. Unlike oil in its natural form, supplementation with capsules was not effective [R].

Scientists are investigating whether oleic acid, the main fatty acid found in olive oil, excites neurons that cause weight loss (POMC) [R].

Berberine

Berberine is an alkaloid with potent metabolic effects. People use berberine as a supplement to support weight control and glucose metabolism, and it has been found to decrease IL-6 in rats [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].

People with high-expression IL6 or IL6R variants may benefit from berberine, which decreased IL-6, enhanced leptin sensitivity, and improved weight loss symptoms in various studies.