weight & body fat

nutrition

ADIPOQ

The Genetic Link Between Adiponectin and Obesity (ADIPOQ)

Written by Carlos Tello, PhD on June 4th, 2020

ADIPOQ encodes the protein hormone adiponectin, a key regulator of fat and sugar metabolism. Several variants of this gene are associated with obesity and insulin resistance — read on to check your genes and get tailored tips.

What Is the ADIPOQ Gene?

The ADIPOQ gene, also known as APM1 (short for ‘adipose most abundant gene transcript 1’), encodes the protein hormone adiponectin. This hormone is the most abundant gene product of fat cells and acts as a messenger molecule in other tissues, especially in the muscles and liver [R, R].

By activating multiple pathways in these tissues, adiponectin controls processes such as insulin sensitivity, fat burning, inflammation, and cell death [R, R, R].

Whether low adiponectin levels actually cause these conditions or are just a biomarker for their onset and progression remains unknown, but the production of this hormone is reduced in people with [R, R, R, R]:

Obesity
Heart disease
Diabetes
Asthma
Preterm birth

Conversely, high adiponectin levels have been associated with autoimmune diseases such as rheumatoid arthritis, osteoarthritis, and lupus [R, R].

The ADIPOQ gene encodes the protein hormone adiponectin. Variations in its levels are associated with different metabolic and immune conditions.

Adiponectin in Fat and Sugar Metabolism

Adiponectin stimulates the development of fatty cells and promotes the ‘healthy’ expansion of the fatty tissue. While its overproduction caused obesity in engineered mice, it also protected against insulin resistance resulting from a high-fat diet [R, R, R].

In response to energy starvation in muscle cells, adiponectin activates the fat-burning enzyme AMPK and pathways that promote sugar uptake. This results in increased energy expenditure and weight loss, as well as contributing to lower blood sugar levels [R, R, R, R, R].

In the liver, adiponectin alleviates fatty liver disease (both alcohol- and obesity-associated) by activating fat breakdown while blocking its production through the AMPK and PPAR-α pathways [R, R, R].

Importantly, the liver plays a key role in regulating blood sugar levels by maintaining a balance between its production and transport. Adiponectin is involved in these processes by blocking the enzymes that produce glucose in the liver and enhancing the sensitivity of its tissues to insulin [R, R].

Adiponectin plays key roles in fat and sugar metabolism, mainly by promoting fat burning and enhancing insulin sensitivity.

ADIPOQ Variants in Body Weight and Insulin Resistance

Rs1501299

Body Weight

The minor ‘T’ variant of rs1501299 was associated with increased BMI and risk of obesity in several studies on Italian, African American, Mexican, Finnish, Tunisian, Greek,Taiwanese, and Indian populations. Similarly, obese carriers of this variant had higher fat percentage in a Swedish study [R, R, R, R, R, R, R, R, R, R].

However, the allele had no relationship with BMI in studies on Chinese, Jordanians, and diabetic Japanese. In Greek women with PCOS, Czech women, and healthy Tunisian volunteers, it was even associated with lower BMI and insulin levels [R, R, R, R, R, R].

All in all, the evidence points towards an association with body weight. Indeed, a meta-analysis of 18 studies concluded that this variant increases the risk of obesity in people of Caucasian ethnicity [R].

Insulin Resistance

The ‘T’ variant has been associated with increased insulin resistance and risk of type 2 diabetes and metabolic syndrome in Italian, Indian, and Spanish studies [R, R, R, R].

How It Works

The minor variant at rs1501299 has been associated with increased adiponectin levels in multiple studies on Italian, Chilean, Chinese, Korean, Portuguese, French Caucasian, and Cypriot populations [R, R, R, R, R, R, R].

However, the variant had no effect on adiponectin levels in a Japanese study and even reduced them in Italian and South Indian studies [R, R, R].

The minor variant of rs1501299 may increase adiponectin levels and has been associated with obesity and insulin resistance, especially in Caucasians.

Rs2241766

Body Weight

The minor ‘G’ variant of the rs2241766 polymorphism was associated with obesity in Mexicans, French, Japanese, female Amerindians, young Greeks, and Chinese children. In obese Japanese men, carriers had higher levels of abdominal fat [R, R, R, R, R, R, R].

However, it protected against obesity in Belgian women, French Canadians, and American Hispanics, and was associated with lower waist circumference in a Swedish study [R, R, R, R].

In any case, this polymorphism was most commonly unrelated to obesity, as seen in multiple studies on Mexican, African American, Chinese, Italian, British, Greek, Danish, Tunisian, and Korean populations [R, R, R, R, R, R, R, R, R].

A meta-analysis of 18 studies concluded that this polymorphism isn’t linked to obesity risk, but another one found an association only in Chinese studies. However, the authors of the second review warned that larger, better-designed studies were needed to confirm their findings [R, R].

Insulin Resistance

The minor ‘G’ variant was associated with reduced glucose tolerance in a Spanish study and with excess blood sugar in French [R, R].

In line with this, it increased the risk of type 2 diabetes in Japanese, Egyptian, and Finnish populations [R, R, R].

Similarly, this variant was associated with metabolic syndrome in Chinese adults and adolescents [R, R].

How It Works

The minor ‘G’ variant was associated with higher adiponectin levels in obese Canadian, Japanese, and Greek, as well as in healthy Caucasians, and Danish women [R, R, R, R, R, R].

However, it had no connection with adiponectin levels in two studies on Japanese and French Caucasians, and was even associated with lower levels of this hormone in Chinese children and adolescents [R, R, R, R].

The minor variant of rs2241766 may increase adiponectin levels. Preliminary research associated it with obesity (mainly in Chinese) and with insulin resistance.

Rs17300539

Body Weight

The minor ‘A’ allele of rs17300539 was associated with obesity in Tunisian, French, Italian, and Croatian populations [R, R, R].

However, the variant was unrelated to obesity in Polish children and Southern Italians. Moreover, a study on Caucasian Americans associated this variant with reduced weight and lower waist and hip circumferences [R, R, R].

Nevertheless, a meta-analysis of 18 studies concluded that the minor variant increases the risk of developing obesity in Caucasians [R].

Insulin Resistance

In French children, the ‘A’ variant was associated with higher fasting insulin levels and increased risk of insulin resistance [R].

Similarly, it was associated with an increased risk of metabolic syndrome in Croatian adolescents [R].

In contrast, the major ‘G’ variant increased the risk of insulin resistance and metabolic syndrome in an obese Spanish population [R].

How It Works

This polymorphism is located in the gene region that controls its expression (the promoter). Studies have consistently shown that the minor variant increases ADIPOQ expression and blood adiponectin levels [R, R, R, R, R].

The minor variant of rs17300539 increases adiponectin levels. Preliminary research associates it with obesity, especially in Caucasians. Its link with insulin resistance is more controversial.

Rs266729

Body Weight

The minor ‘G’ variant of rs266729 has been associated with an increased risk of obesity and higher body weight in Korean, Chinese, Finnish, and Arab adults, Swedish diabetics, Croatian adolescents, and Polish children [R, R, R, R, R, R, R].

In male Cypriots, it was associated with slightly higher chances of becoming overweight, but not obese [R].

However, this association couldn’t be found in studies on Caucasian Americans, African Americans, Southern Italians, and Polish children. A study on French Caucasians even associated this variant with a reduced risk of obesity [R, R, R, R, R].

A meta-analysis of 18 studies concluded that this variant reduces obesity risk only in Asians [R].

Insulin Resistance

The minor ‘G’ variant was associated with insulin resistance in two studies on Irish and French populations [R, R].

It also increased the risk of type 2 diabetes in Swedish and obese Chinese, and metabolic syndrome in Croatian adolescents [R, R, R].

Diabetic carriers of this variant had an increased risk of developing NAFLD in a Taiwanese study [R].

However the ‘G’ variant was associated with a reduced risk of diabetes in Finnish and Germans, and with increased insulin sensitivity in American children [R, R, R].

How It Works

This polymorphism is located in a gene region that controls its expression (the promoter). The minor variant has been associated with lower adiponectin levels in American Caucasians, Southern Italians, Cypriots, Polish children, and Taiwanese diabetics [R, R, R, R, R].

However, this variant didn’t affect adiponectin levels in two studies on Pakistani and South African populations [R, R].

The minor variant of rs266729 may reduce adiponectin levels. It has been associated with obesity, especially in Asians. Results on its potential association with insulin resistance are mixed.

Your ADIPOQ Results for Body Weight

SNP Table

variant	genotype	frequency	risk allele
rs1501299
rs2241766
rs17300539
rs266729

SNP Summary and Table

Primary SNP:

ADIPOQ rs1501299

‘G’ = normal rates of obesity
‘T’ = increased rates of obesity (especially in Caucasians) and insulin resistance
Approximately 50% of the world population carries two copies of the ‘G’ allele
The ‘T’ variant is slightly more common in African descendants and less in people with a South Asian background

Other Important SNPs:

ADIPOQ rs2241766

‘T’ = normal rates of obesity
‘G’ = increased rates of obesity (especially in Chinese) and insulin resistance
95% of the world population carries the ‘T’ allele
The ‘G’ variant is especially rare in people of African ancestry and slightly more common in those of East Asian ethnicity

ADIPOQ rs17300539

‘G’ = normal rates of obesity
‘A’ = increased rates of obesity (especially in Caucasians) and, possibly, insulin resistance
The ‘A’ variant is extremely rare. Less than 1% of the world population carries two copies

ADIPOQ rs266729

‘C’ = normal rates of obesity and increased weight loss
‘G’ = increased rates of obesity (especially in Asians)
Only 6% of the world population has the ‘GG’ genotype

Recommendations

Diet

Low-Calorie, Mediterranean Diet

Calorie restriction is one of the most effective ways to lose weight. Eating low-calorie diets helps reduce fat buildup and food cravings while increasing adiponectin levels and fat burning [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].

The minor ‘T’ variant of rs1501299 was associated with decreased weight loss and reduced improvements in insulin resistance, adiponectin levels, and blood fat profile in response to low-calorie Mediterranean diets in several studies [R, R, R, R].

A Spanish study associated the minor ‘G’ variant of rs2241766 with increased weight gain over a 3-year period. However, the effect was reversed with a low-calorie Mediterranean diet [R].

The major ‘G’ variant of rs17300539 increased the risk of insulin resistance and metabolic syndrome in an obese Spanish population, but the effect was reduced during a period in which the participants ate a low-calorie diet. However, the beneficial effect wasn’t sustained after the dietary intervention [R].

The major ‘C’ variant of rs266729 increased weight loss in Taiwanese who reduced their dietary calories by taking an appetite suppressant (sibutramine) [R].

This variant was also associated with increases in adiponectin levels and decreases in LDL-cholesterol and insulin after weight loss from dietary interventions in several Spanish studies [R, R, R].

Unsaturated Fats

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. In a large meta-analysis of 21 clinical trials, fish oil in combination with lifestyle changes significantly reduced waist-to-hip ratio [R, 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 fat breakdown and insulin sensitivity by promoting adiponectin secretion, as shown in two meta-analyses [R, R, R, R].

An olive oil-enriched diet brought about greater weight loss than a lower-fat diet in an 8-week comparison. Dietary olive oil increased adiponectin levels in a small trial on 17 obese women [R, R, R].

Although the minor ‘A’ allele of rs17300539 has been associated with obesity in Caucasians, it reduced obesity when combined with high dietary monounsaturated fatty acids in a study from the US. It’s important to note, however, that the main dietary source of these fatty acids was probably not olive oil as would be expected in Mediterranean countries [R].

Intermittent Fasting

Different intermittent fasting modalities such as alternating fasting and refeeding and time-restricted feeding increased adiponectin levels in several studies. However, the effects of Ramadan fasting on this hormone remain unclear and the results of different studies are mixed [R, R, R, R, R, 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. In a clinical trial on 52 women, caloric intake after 8:00 PM increased the risk of obesity [R, R].

Coffee

A meta-analysis of 12 studies associated coffee consumption with higher blood adiponectin levels [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].

Chilly Peppers

Capsaicin (both dietary and applied on the skin) increased adiponectin levels and promoted weight loss in mice [R, R, R, R].

Capsaicin is found in chili peppers and is responsible for their spicy flavor. This molecule activates receptors (TRPV1) that may speed up metabolism, increase energy expenditure, and reduce appetite [R, R, R, R].

Resistant Starch

In a clinical trial on 15 healthy volunteers, including resistant starch (barley-kernel bread) in the diet increased adiponectin levels and improved glucose tolerance. Dietary resistant starch also increased adiponectin levels in mice and rats [R, R, R, R].

Some evidence from animal studies suggests that resistant starchmay help promote weight loss. It reduces fat accumulation and blood glucose levels and increases the breakdown of fat through fermentation in the intestines, thus potentially improving weight control [R, R, R].

Food sources of resistant starch include whole grains, seeds, legumes, and starchy vegetables (such as potatoes) and fruits (such as bananas).

There are supplemental powders online (hi-maize) that also contain high levels of resistant starch.

Low-calorie diets help lose weight, especially in people carrying certain ADIPOQ variants. Practicing intermittent fasting and including healthy fats, coffee, spicy foods, and resistant starch in the diet may also help lose weight while increasing adiponectin activity.

Lifestyle

Exercise

Caucasian women carrying the minor ‘T’ variant of rs1501299 experienced higher weight and fat loss in response to a 12-week training program. Similarly, metabolic syndrome patients with this variant showed higher reductions in waist circumference, insulin resistance, blood pressure, and glucose and triglyceride levels after an intervention combining exercise and a special diet [R, R].

The major ‘C’ variant of rs266729 was associated with an increased weight and LDL-cholesterol reduction in response to exercise in a study on Polish women [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].

Exercise helps reduce weight by increasing energy expenditure. Variants at certain ADIPOQ polymorphisms may alter the effects of exercise on weight loss and blood parameters.

Supplements

Berberine

In people with metabolic syndrome, supplementation with berberine reduced the leptin to adiponectin ratio. Berberine increased adiponectin levels in mice fed high-fat and high-fructose diets [R, 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].

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 3 clinical trials on obese and overweight people, CLA supplementation increased blood adiponectin levels [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].

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

Supplementation with resveratrol increased adiponectin levels in clinical trials on people with heart disease, excess weight, and NAFLD [R, R, 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 accomplished this by turning off genes that cause weight gain and blocking fat-creating enzymes while activating genes that enhance energy use and mitochondrial health [R, R].

Green Coffee Extract

In a clinical trial on 64 obese women, green coffee extract combined with calorie restriction increased blood adiponectin levels while reducing body weight and blood fats. However, the extract failed to modify adiponectin levels in people with NAFLD [R, R].

Chlorogenic-acid enriched green coffee extract increased weight loss and fat burning while lowering blood fat and sugar levels in multiple clinical trials [R, R, R, R, R, R, R].

However, dark-roast (low in chlorogenic acid) coffee reduced weight more effectively than light-roast coffee in a clinical trial on 30 healthy people [R].

Garcinia

In multiple clinical trials, Garcinia cambogia reduced weight and body fat. A review of 12 studies found that, on average, supplementation with Garcinia was associated with weight loss of about 2 pounds (0.88 kg) over several weeks [R, R, R, R, R, R, R, R, R].

Its active compound hydroxycitric acid activated the fat-burning adiponectin-AMPK pathway in chicken [R].

Yerba Mate

Supplementation with yerba mate reduced body fat mass, body fat percentage, and waist-to-hip ratios in 30 obese participants. In another study on 14 healthy volunteers, taking it before exercise increased fat breakdown and energy expenditure [R, R].

In mice, yerba mate decreased food intake, fat buildup, energy use, and the blood levels of cholesterol, triglycerides, and sugar while increasing adiponectin levels and activity [R, R, R].

Supplementing with berberine, CLA, resveratrol, green coffee extract, garcinia, and yerba mate may help lose weight and increase adiponectin levels.

Carlos Tello

PhD

Carlos received his PhD and MS from the Universidad de Sevilla.

Carlos spent 8 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and lay audiences. He strongly believes that scientific literacy is crucial to maintaining a healthy lifestyle and avoiding falling for scams.

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.

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What Is the ADIPOQ Gene? ADIPOQ Variants in Body Weight and Insulin Resistance Your ADIPOQ Results for Body Weight

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The Genetic Link Between Adiponectin and Obesity (ADIPOQ)

What Is the ADIPOQ Gene?

Adiponectin in Fat and Sugar Metabolism

ADIPOQ Variants in Body Weight and Insulin Resistance

Rs1501299

Body Weight

Insulin Resistance

How It Works

Rs2241766

Body Weight

Insulin Resistance

How It Works

Rs17300539

Body Weight

Insulin Resistance

How It Works

Rs266729

Body Weight

Insulin Resistance

How It Works

Your ADIPOQ Results for Body Weight

SNP Table

SNP Summary and Table

Recommendations

Diet

Low-Calorie, Mediterranean Diet

Unsaturated Fats

Intermittent Fasting

Coffee

Chilly Peppers

Resistant Starch

Lifestyle

Exercise

Supplements

Berberine

Conjugated Linoleic Acids

Resveratrol

Green Coffee Extract

Garcinia

Yerba Mate

Disclaimer

More weight & body fat blogs

More nutrition blogs

Content

Unlock Personalized Results And So Much More!

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Men's Health Month 10% Off

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Men's Health Month 15% Off

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