Adiponectin

It is well documented that obesity is associated with an increased risk of cardiovascular disease and higher overall mortality. Obesity also correlates with increased risk of Alzheimer’s disease and many types of cancer. It has been estimated that severe obesity may shorten lifespan by up to ten years (1). This is comparable to the effect of smoking.

Obesity is usually defined as an elevated body mass index (BMI). It is characterized by the accumulation of fat in our body.

Adiponectin

But, what’s wrong with walking around with some extra weight? Why is excess body weight associated with increased risk of heart disease, cancer and premature death?

When we discuss obesity, we often tend to look primarily at body weight itself. This may be misguided. In fact, body fat does much more to our health than take up space and increase weight.

Fat cells are biologically active, and their function or dysfunction may affect our health in many ways. For example, fat cells produce and secrete important biologic substances. One of these substances is called adiponectin. In fact, adiponectin could represent one of the missing links between obesity and increased risk of diabetes, heart disease, and cancer.

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Adipose Tissue

The body can store extra energy as fat in adipose tissue. Adipose tissue is a loose connective tissue that is mainly composed of cells called adipocytes. It is is mainly located beneath the skin (subcutaneous fat) and around the internal organs (visceral fat).

It is possible to assess how much of our body weight is composed of fat. Although it may vary a lot, men and women of normal weight have about 15 percent and 30 percent body fat respectively.

Adipose tissue appears to be an important endocrine organ. It produces hormones such as leptin and estrogen as well as cytokines that play an important role for cell signaling. Cytokines secreted by adipose tissue are called adipokines.

Visceral Fat and Subcutaneous Fat

Body shape and the regional distribution of fat appear more important for health than the total amount of adipose tissue. For example, it has been shown that the accumulation of fat around the internal organs may be more harmful than fat accumulation elsewhere. Excess accumulation of this type of fat is termed visceral obesity.

pierre-auguste_renoirIn the 1940s, Professor Jean Vague from the University of Marseille noted that women normally had twice as much fat mass as men (2). However, he also found that the metabolic complications associated with obesity were much less common among women than men.

Vague defined two different body shapes. Android obesity or apple shape refers to the accumulation of fat in the upper body are. Gynoid obesity or pear shape refers to the accumulation of fat on the hips and thighs. The latter is more common among women than men. This is very well demonstrated in Pierre-Auguste Renoir’s painting above.

Visceral fat accumulation is associated with insulin resistance, high blood pressure, high levels of triglycerides, low levels of HDL-cholesterol, small dense LDL particles, and increased risk of diabetes and cardiovascular disease.

However, subcutaneous fat appears much more innocent than visceral fat. In fact, recent studies suggest that abdominal subcutaneous fat is not associated with risk factors for cardiovascular disease (3). This suggests a possible protective effect of subcutaneous fat.

Adiponectin

In the 1990s, scientists found a protein secreted by adipocytes and named it adiponectin (4).

Although adiponectin is secreted only from adipose tissue, the plasma concentration of adiponectin is much lower in obese subjects than in non-obese healthy volunteers.

Plasma levels of adiponectin are especially low in individuals with visceral obesity. It is believed that adiponectin deficiency may play an important role for many of the negative metabolic consequences of visceral fat accumulation. The clinical term for low plasma levels of adiponectin is hypoadiponectinemia.

So, although adiponectin is produced by adipose tissue, its production is abnormally low in obese individuals, in particular, those with visceral obesity.

Some adipokines may negatively affect health. For example, many adipokines are pro-inflammatory and may support chronic low-grade inflammation in the body. On the other hand, adiponectin is protective and appears to reduce inflammation.

Studies show that low levels of adiponectin are associated with raised levels of several different markers of inflammation (5).

Adiponectin and Obesity

Obese people have lower blood levels of adiponectin than normal weight individuals (6,7). Furthermore, reduction of obesity increases adiponectin levels (8,9).  Overall, it appears that losing weight through diet, exercise, medications and surgery will increase adiponectin levels in blood.

Low adiponectin levels are more strongly associated with the amount of visceral fat than subcutaneous fat (10).

Development of subcutaneous fat is is an active process in infancy, adolescence and pregnancy (11). In middle aged and elderly people, over nutrition does not lead to an effective storage of energy as subcutaneous fat (12). Instead, visceral fat accumulation becomes more common.

Lifestyle factors such as overeating and physical inactivity in young and middle-age appear to increase the risk of visceral obesity.

Dysfunction of adipose cells is more common in visceral fat tissue than subcutaneous fat tissue. Such dysfunction may cause an unbalance in the production of adipokines leading to overproduction of offensive adipokines and under production of defensive adipokines such as adiponectin (11).

Adiponectin, Insulin Resistance and Type 2 Diabetes

Obesity is associated with high prevalence of insulin resistance and type 2 diabetes.

Several clinical studies have shown that low production of adiponectin correlates with the development of insulin resistance and type 2 diabetes (13).

Adiponectin appears to promote an insulin-sensitizing effect (14). It has been suggested that downregulation of adiponectin could be a mechanism whereby obesity could lead to insulin resistance and diabetes. Thus, in theory, increasing the availability of adiponectin might reverse insulin resistance and thereby decrease the risk of diabetes.

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Adiponectin and Lipid Abnormalities

High levels of triglycerides and low levels of HDL cholesterol are commonly found in people with obesity or metabolic syndrome. High triglyceride/HDL cholesterol ratio is associated with increased risk of cardiovascular disease.

Adiponectin levels correlate positively with HDL-cholesterol and negatively with triglycerides.

Experimental studies have suggested that adiponectin promotes synthesis of HDL cholesterol (15).

Therefore, low levels of adiponectin may be important for some of the lipid abnormalities associated with obesity.

Adiponectin and Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is common among people with obesity. It may increase the risk for liver cirrhosis and cancer of the liver.

NAFLD has been associated with low levels of adiponectin in clinical studies (16). Low adiponectin levels correlate with the severity of fat accumulation in the liver (17).

Experimental studies have found that adiponectin antagonizes excess lipid storage in the liver (18).

Adiponectin and Cancer

Obesity is associated with increased risk of cancer. This relationship has been highlighted by the US National Cancer Institute.

Several studies suggest that adiponectin may play a role in cancer. Low plasma levels of adiponectin have been linked to some types of breast cancer (19), endometrial cancer (20), prostate cancer (21) and colorectal cancer (22).

It is not known whether adiponectin deficiency plays a causative role when it comes to cancer risk. Furthermore, it has not been shown that increasing adiponectin levels will reduce the risk of cancer.

Adiponectin and Coronary Artery Disease

Several studies suggest that reduced levels of adiponectin are associated with higher prevalence of coronary artery disease (23) and higher risk of heart attack (myocardial infarction)(24).

Studies also suggest that low levels of adiponectin may be predictive of future coronary events (25).

Animal studies indicate that adiponectin administration may protect heart muscle cells from injury from loss of blood flow (26)

Clinical Use of Adiponectin Measurements

Adiponectin circulates in relatively high concentrations in blood and is easily measured. However, the use of adiponectin measurements has so far been confined to clinical trials and has not yet spread into clinical practice. Nevertheless, the potential to use adiponectin as a biologic risk marker certainly exists.

Adiponectin concentrations might also be used to decide on the aggressiveness of interventions and to monitor treatment. For example, it has been suggested that adiponectin levels may be used to monitor the efficacy of interventions in patients with metabolic syndrome (27).  Other studies suggest that adiponectin levels may be used to monitor the anti-inflammatory effects of statin therapy (28). Change in adiponectin levels may also reflect the metabolic effects of diabetes therapies (29).

Reference Values for Adiponectin

The Mayo Clinic (Mayo Medical Laboratories) has presented the following reference ranges for adiponectin measurements in blood.

Body Mass IndexAdiponectin mcg/mL
Body Mass Index <25Males 4-26
Females 5-37
Body Mass Index 25-30Males 4-20
Females 5-28
Body Mass Index >30Males 2-20
Females 4-22
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Adiponectin as a Therapeutic Target

The favorable effects of adiponectin could be increased either by directly administering adiponectin by injection or by using treatment that increases its plasma levels.

Manufactured adiponectin has been administered by infusion in animal studies. However, the molecular complexities of adiponectin have made its production as a therapeutic agent difficult (30). Scientists are also looking at agents that could enhance adiponectin secretion from adipose tissue or mimic adiponectin effects on its receptors (31).

Statins, thiazolidinediones, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are examples of pharmaceutical drugs that have been found to elevate circulating levels of adiponectin.

Studies have also found that nutraceutical compounds such as fish oil, safflower oil, conjugated linoleic acid, grape-seed extract, green tea extract, taurine and resveratrol are able to elevate plasma levels of adiponectin (32).

Losing weight, caloric restriction and physical exercise (33) can raise adiponectin levels.

Recently, phenolic compounds such as raspberry ketones have been marketed for weight loss. One of their proposed mechanisms of action is to raise adiponectin levels. However, there is no clinical evidence for such an effect in humans.

The Take-Home Message

Adiponectin is a protein secreted by adipose tissue. Adiponectin levels are lower among obese people than those who are normal weight. Visceral fat accumulation is associated with lower adiponectin levels than subcutaneous fat accumulation.

Low adiponectin levels may reflect dysfunction of adipose tissue among obese individuals.

Low levels of adiponectin are associated with inflammation, lipid abnormalities, insulin resistance and increased risk of diabetes, NAFLD, coronary heart disease, and cancer. A causative role of adiponectin remains to be proven.

Although adiponectin may be used as a biologic marker to assess risk and monitor treatment, adiponectin measurements are seldom performed in clinical practice.

Lifestyle interventions, some pharmaceutical drugs, and a few nutraceutical compounds may raise adiponectin levels.

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Travis J
Travis J
5 years ago

This completely overlooks all of the thin people who suffer from all the same conditions: type 2 diabetes, heart disease, etc. That alone makes it unlikely that adiponectin is a causal agent, if it is that closely correlated with body fat.

Axel F Sigurdsson
Admin
Axel F Sigurdsson
5 years ago
Reply to  Travis J

Thanks Travis.
There’s limited data on adiponectin and risk among normal weight individuals.
However, although thin people and people with normal adiponectin levels suffer from diabetes and heart disease, the risk of these disorders is much higher among the obese, in particular those with low adiponectin levels. So in theory, adiponectin could explain the increased risk among obese people although it’s not a causal factor among those who are normal weight (other factors might play a bigger role in normal weight people).
But you’re right, a causative role for adiponectin reamins to be proven.

jen
jen
5 years ago

Wondering what medications can raise adiponectin levels??? can’t find anything online. My teen daughter has low levels and high leptin indicating adipose tissue insulin resistance combined with familial hypercholesterolemia. taking her to see an endocrinologist soon but want all the info prior to ask questions.

Diane
Diane
5 years ago

I used to have a weight and BMI that was WNL but due to a severe lung issue have had to be on prednisone in high doses off and on for last 4 years, end result was me gaining 75lbs and am now Type II diabetic. I recently saw a supplement that contained adipolectin that stated with diet and exercise, may help with losing some of the weight. Should I try it? Can there be a risk to taking it? Thank you sincerely. Please reply ti my email below….I really appreciate your help/advice. Sincerely, Diane

Axel F Sigurdsson
Admin
Axel F Sigurdsson
5 years ago
Reply to  Diane

Hi Diane

Sorry to hear about your health problems. Unfortunately there’s no evidence that such supplements will help. I wouldn’t recommend them under any circumstances.

Axel F Sigurdsson
Admin
Axel F Sigurdsson
5 years ago
Reply to  Travis J

It’s important to understand that supplements containing adiponectin (if they really do that) are unlikely to work or to raise blood levels of adiponectin. Adiponectin is a protein and is not easily absorbed from the intestine. Digestive enzymes will probably break it into amino acids. So adiponectin can not be administered through the oral route.

Several substances may increase the body’s own production of adiponectin. Among them are compounds such as fish oil, safflower oil, conjugated linoleic acid, grape-seed extract, green tea extract, taurine and resveratrol.

nick
nick
5 years ago

interesting…….. what about BAT and cold thermogenisis to increase adiponectin ?

currently there are a few products available used for this, i use a vest with ice packs placed over the BAT around neck/sternum/upper back. Kicks me into ketosis quick. Fatloss sells, but heck after reading the above list i wonder if the medical fraternity is looking into cold thermogenis as a route to elevated adiponectin and health?

ART
ART
5 years ago

How is it possible to increase the adiponectin level to help lose weight?

Axel F Sigurdsson
Admin
Axel F Sigurdsson
5 years ago
Reply to  ART

The best way to increase adiponectin levels is to lose weight 🙂

John Funk
John Funk
5 years ago

to Lose weight and increase adiponectin get Arctic Ruby Oil, Calanus.see pubmed/ 2013 Dec, and 2014 Feb, also check Google.

MindWithAView
MindWithAView
5 years ago

ART: How is it possible to increase the adiponectin level to help lose weight? Axel F Sigurdsson: The best way to increase adiponectin levels is to lose weight 🙂 It is this kind of glib, snarky advice from physicians that drives people away from the medical profession. Despite the very plain fact that losing weight is NOT as easy as eating less and exercising more, physicians still toss off this kind of non-advice and push their patients out the door. You see, the problem is that physicians (and the rest of the population) think like this: When a person eats… Read more »

Axel F Sigurdsson
Axel F Sigurdsson
5 years ago
Reply to  MindWithAView

Thanks for the comment MindWithAView. I was not trying to be witty or snarky as you suggest. I was only trying to give an honest answer. Losing weight is the only known way to significantly increase adiponection levels. As you can read in my article a few nutraceutical compounds such as fish oil, safflower oil, conjugated linoleic acid, grape-seed extract, green tea extract, taurine and resveratrol are may elevate plasma levels of adiponectin. Whether this will be reflected in improved health is unknown. Almost every day I meet people dealing with obesity and the problems that that travel with it… Read more »

MindWithAView
MindWithAView
5 years ago

No one’s looking for “a simple solution”, a magic bullet that will allow people to be lazy and gluttonous and still be thin. Your reply just reveals more about your attitude than you knowledge. You still think “weight is largely the byproduct of behaviors and choices”–the one “sound bite” from Katz’s article that jibes with your prejudicial beliefs regarding obesity. You and other doctors of your ilk have got a very comfortable belief system that allows you to feel virtuous and superior to your obese patients. A system that also allows you an easy out when your exhortations to “diet… Read more »

MindWithAView
MindWithAView
5 years ago
Reply to  MindWithAView

Dr. Sigurdsson, you should also take a look at this, although I know you will probably simply view it and pull out the sound bites that jibe with your prejudice.

In order to stay thin, this woman needed to exercise 3-4 hours daily and eat no more than 1,200 calories daily. Try living like that for a while. Let’s see how long you can do it. Yet thousands of menopausal and post-menopausal women face this dilemma.

https://www.insideedition.com/videos/3758-why-a-mom-of-five-admits-being-fat-makes-her-happy

Axel F Sigurdsson
Axel F Sigurdsson
5 years ago
Reply to  MindWithAView

I can assure you that the sole purpose of my blog and my writings is to inform and to be of help. I also believe that a healthy discussion about issues related to medical matters can be helpful. Therefore I appreciate your interest in my writings and that you take time commenting. Since I started my blog I’ve always highlighted the importance of mutual respect. Usually we don’t know much about the people we are debating with. Making things personal and drawing conclusions about how people think, whether they’re good or bad has no place in such debates. In fact… Read more »

MindWithAView
MindWithAView
5 years ago

I see that you are feeling disrespected, insulted, misunderstood, and misjudged. Do you get that THAT is exactly how your obese patients feel?

Yes, I swung at you pretty hard, but it certainly got the message through. When you make off-hand comments (like, just lose weight!) based solely on biases beliefs regarding the causes of obesity, you will intentionally or unintentionally insult, demean, and falsely blame people.

Take a look at this–just one of many, many studies showing that people differ in terms of fat loss resistance: https://www.ncbi.nlm.nih.gov/pubmed/21470990

And this: https://www.ncbi.nlm.nih.gov/pubmed/22102511

And this: https://www.ncbi.nlm.nih.gov/pubmed/12370112

Axel F Sigurdsson
Axel F Sigurdsson
5 years ago
Reply to  MindWithAView

Still trying to describe how I think and how I feel. Still making it personal? By the way, who said “just lose weight.”Did I say that. I don’t think so. You wrote “THAT is exactly how your obese patients feel”. But I’ve learned through the years that obese patients are just people and they don’t all feel the same. Some may feel “disrespected, insulted, misunderstood” as you suggest, but others don’t. Our feelings are not determined by our body weight. But, I respect your opinion and I think you got your message through. And, in fact I think I may… Read more »

MindWithAView
MindWithAView
5 years ago

I don’t see that you’ve changed your mind about anything. Your responses almost entirely consist of defending yourself against what you perceive to be unjust accusations. Admit it: You still believe, at bottom, that fat people are fat because they eat too much of the wrong things and don’t exercise enough. And the only way to treat obesity is to impress upon these people how important it is to learn to eat right and exercise. And I am sure this is true of some of your overweight patients, while others cling to that false hope because it allows them to… Read more »

Axel F Sigurdsson
Axel F Sigurdsson
5 years ago
Reply to  MindWithAView

I looked at the links. Thanks for drawing my attention to those. Appreciate it.

Alan M.
5 years ago

MindWithAView needs to chill out. Yes, this person did get personal, and Dr. Sigurdsson, you handled yourself very well, better than I would have given the same knucklehead this person obviously is. He/she may have a mind with a view – from an insane asylum.

Maria Jasmine Freeman
Maria Jasmine Freeman
3 years ago
Reply to  MindWithAView

I fully agree about this particular point regarding menopausal women, let alone other points. I personally turned acutely morbidly obese, at the outset of perimenopause, changed in one year from a 4-6 American size, to 14-16( with fat gain and edema), while I was recalcitrantly vomiting-daily, and having( non infectious diarrhea, just hormonal). Unfortunately, I did not measure my Adinopectin level, for one reason, and another, to make a judgment. Only few years therefrom, on no Hormonal treatment, or any pharmacological intervention anyway, I reclaimed a 6-8 American size, while indeed my vomiting and diarrhea ameliorated, poniting perhaps to some… Read more »

Raghbir
Raghbir
5 years ago

Does any one know name of the test to check adiponectin level?

Axel F Sigurdsson
Axel F Sigurdsson
5 years ago
Reply to  Raghbir

Raghbir.
I think it’s just plasma – adiponectin or serum – adiponectin.

A. T.
A. T.
4 years ago

I have low adiponectin level of around 3.5 (32yo white male) but I’m not overweight. My BMI jumped from ~19 to ~23 a few years ago but has remained fairly constant after that. I read a few papers online and this summary, and it made me a bit confused. The evidence seems to exclude people like me who are not overweight and have low adiponectine. My glucose level has been creeping up from ~80 to ~130 during the past few years (supporting pre-diabetic scenario) and I have consistently had the high-triglyceride-low-HDL mentioned here, which is not responsive to any amount… Read more »

Axel F Sigurdsson
Axel F Sigurdsson
4 years ago
Reply to  A. T.

A.T.

The bulk of our knowledge of low adiponectin levels and its association with risk is in the context of obesity. We know much less about the role of adiponectin in normal weight individuals like yourself.

High triglyceride/HDL cholesterol ratio can reflect insulin resistance and so could the glucose levels. I assume you’ve had your HbA1c measured https://www.docsopinion.com/2015/07/20/hba1c-and-diabetes-glycated-hemoglobin-explained/

Low adiponectin levels have been addociated with insulin resistance in some studies.

A. T.
A. T.
4 years ago

Thank you for your response and the informative article. I’ve had HbA1c measured twice last year, before and after a 3-month targeted exercise program, to see the effect of exercise on my lipid profile. I did 30-min sessions of aerobic and weight training 6 days a week without missing a single day. No changes in diet. My endocrinologist was not concerned about glucose at the time. My glucose levels were 95 and 94, and HbA1c was 5.1% and 5.2% respectively. So, basically borderline high glucose levels were unaffected by exercise in my case. Since last year, glucose levels have gradually… Read more »

Anne
Anne
4 years ago

Dr. Sigurdsson,
I happen upon your blog while looking for data on my own research, the dysfunction of adiponectin secretion in obesity. As a researcher, I sometimes struggle to explain my work in coherent manner. Thank you for doing a wonderful job of explaining the limited knowledge we have on the correlation between adiponectin and obesity. Hopefully we’ll be able to add more knowledge soon.

Axel F Sigurdsson
Axel F Sigurdsson
4 years ago
Reply to  Anne

Thank you very much Anne.
I appreciate your interest.
Good luck with your research.
Axel

Maria Jasmine Freeman
Maria Jasmine Freeman
4 years ago

Although late reading it after so long, I think this article is fascinating, and reflects the great effort exercised by the author; thanks. Underlining the role of adinopectin in human physiology, adding to scientific research for controlling associated disorders, it also highlights the point that our body is not only one hormone but many, and it is the amazing intricate balance of all-some of them not unveiled yet-that keeps our body in order.

Linda
3 years ago

A few years ago, I joined a gym and used the weights, stair-stepper and treadmill for an hour, 3 days a week for 6 months. I did not lose even one pound, not even half of one pound. Frustrated, I quit the gym and now just walk for an hour maybe once a week, if that. I’m 65 and hypothyroid and can’t seem to lose weight no matter what I do. It’s so frustrating. I take CLA and use Omega-3 oils in cooking. Now looking into raising my adiponectin level but I must admit, I’m skeptical.

Maria Jasmine Freeman
Maria Jasmine Freeman
3 years ago
Reply to  Linda

Hi Linda
I believe you are monitoring your thyroid function tests, free T4, freeT3, and TSH, to ensure you are not still hypothyroid- which explains then, at least partially, your inability to lose weight.
Dr Hana Fayyad, pediatrician

Debbie
Debbie
4 years ago

Hello! Thanks for publishing this; it explained some things I was looking for. However, I can’t seem to find much information on *high* levels of adiponectin. Frankly speaking, I’m obese—not BMI-wise, but in body composition. Oddly enough, every time I get labs done, they come back the same: everything is *very* low: my entire lipid panel, C-peptide, blood pressure. However, my thyroid, glucose, and insulin is normal (suggesting diabetes 1 or 2 is ruled out). This last two panels had, my adiponectin level listed as high. Even though I have a “thyroid” body type (for the lack of a better… Read more »

dr jahanzab
dr jahanzab
4 years ago

hello Dr Axel F Sigurdsson !! i want toknow about the effect of sweet potato on adiponetin leevels

Judy Woods
Judy Woods
11 months ago

Thank you for your info Dr.
Question for you, I have a Adiponectin level of 64.8 with normal on my test result being less than 28.0 Should I be concerned and try to lower it Dr?

Thank you

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