The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 12 No. 6 • October 2009

New Research Focuses on Important
Protective Protein Released by Fat Cells: Adiponectin

Increasing Plasma Adiponectin Levels for Improved
Endothelial Function and Decreased Risk of
Cardiovascular Disease

Adipose (fat) tissue is now known to be much more than a store of fats. Adipose cells release a large variety of active factors called adipocytokines, among which adiponectin is the only one which has been shown to have anti-atherogenic and antiinflammatory properties1,11 and is a potential regulator of lifespan in humans.9 The good news is that increased consumption of n-3 polyunsaturated fatty acids (eicosapentaenoic acid and docosahexaenoic acid, which are found in fatty fish oils) have been shown to significantly increase adiponectin plasma levels in obese humans,1 obese mice,1 and healthy humans.2 In another study of healthy humans,3 a higher ratio of n-3 fatty acids/saturated fats was associated with higher circulating adiponectin levels.

A further paper10 on dietary factors and plasma adiponectin concentrations in men revealed that “[m]oderate alcohol intake is associated with higher adiponectin concentrations, whereas a carbohydrate-rich diet with a high glycemic load is associated with lower adiponectin concentrations in men with no history of cardiovascular disease.”

In another study,13 22 cardiovascular disease patients (12 had had a previous heart attack, while the other ten had stable angina pectoris) drank either Oolong tea or water as the only allowed beverage for a month in a cross-over design. Oolong tea (but not water) consumption resulted in a significant increase in adiponectin levels as compared to baseline.

Health Benefits of Increased Adiponectin

Adiponectin levels are known to be decreased in obese humans.1 High plasma levels of adiponectin have been reported to be associated with reduced risk of heart attack in men,4 to reduce inflammation in adipose tissue,5 and to ameliorate obesity-related hypertension in obese mice treated with adiponectin.6 Decreased plasma concentration of adiponectin levels were reported in hypertensive men with coronary artery disease as compared to normotensive healthy subjects.7 Moreover, low levels of adiponectin were closely associated with endothelial dysfunction in a study of 76 Japanese subjects without a history of cardiovascular disease.8 As macrophages are involved in an important part of the atherosclerosis process (by forming foam cells), the fact that adiponectin has been shown to decrease the release of pro-inflammatory factors by macrophages11 could be, at least in part, one reason that adiponectin is protective against atherosclerosis.

Suppression of Fat Accumulation on a High Fat/High Sucrose Diet

One interesting recent paper12 reports that overexpression of human adiponectin in transgenic mice resulted in suppressed fat accumulation and prevention of premature death from a high-calorie diet. The researchers created a transgenic mouse expressing human full-length adiponectin in the liver to investigate the effects of adiponectin when transgenic and wild-type animals were fed either a normal lab chow diet or a high calorie diet. The mice that had overexpressed human adiponectin, when maintained on a high fat/high sucrose diet had significantly decreased weight gain with less fat accumulation and smaller adipocytes (which have greater insulin sensitivity than large adipocytes) in both visceral and subcutaneous body fat as compared to the wild-type mice on the same diet. Macrophage infiltration into adipose tissue (the source of proinflammatory cytokines) was markedly suppressed by overexpression of adiponectin. Moreover, the mice with overexpressed human adiponectin had an approximately twofold increase in lifespan on the high fat/high sucrose diet as compared to the wild-type mice on the same diet (most wild-type mice fed that diet died at about 1 year of age). The transgenic mice even had a longer lifespan on the conventional low-fat lab chow as compared to the wild-type mice on the same diet.

Possible Effects on Human Lifespan

As mentioned above, adiponectin is a potential regulator of lifespan in humans.9 In the lifespan study,9 researchers studied adiponectin levels in centenarians, their offspring, and unrelated participants. Adiponectin levels were significantly higher in those over 95 as well as in their offspring, suggesting the involvement of genetic factors. The authors report: “Over-representation of two common variants in Adiponectin genes (ADIPOQ) in male long-lived individuals combined with their independent association with elevated plasma adiponectin levels (in men and women) suggests that their presence may promote increased lifespan through the regulation of adiponectin production and/or secretion.”

Do-It-Yourself Adiponectin Therapy: Increased Adiponectin with n-3 Fatty Acids

In the study of the effects of n-3 fatty acid supplementation on adiponectin levels in obese humans,1 for example, the subjects had a significantly increased level of plasma adiponectin concentrations after a 3 month treatment with eicosapentaenoic acid (EPA) (1.8 g per day). In the study of the effects of the ratio of n-6 polyunsaturated fatty acids/n-3 fatty acids on adiponectin levels in healthy humans,2 a ten week intervention resulted in increased adiponectin, reduced LDL, increased burning of fats (lipid oxidation), and reduced plasma levels of TNF-alpha, an inflammatory cytokine. The subjects, who in their usual diets ate less than one fish meal per week, were put on a 10 week dietary intervention that included three fish meals a week and enough canola oil (20 ml a day) to supply 1.7 grams a day of alpha linolenic acid, a shorter chain n-3 fatty acid.

Our Omega-3 HeartFelt™ supplies 1.44 g of EPA and 960 mg of DHA at the highest recommended dose of 8 capsules a day. Both of us take that much. Sandy’s latest lab test for adiponectin was reported as 45, which is very high.

Oolong tea is a component of our ShapeShifter Teas.™


  1. Itoh et al. Increased adiponectin secretion by highly purified eicosapentaenoic acid in rodent models of obesity and human obese subjects. Arterioscler Thromb Vasc Biol 27:1918-25 (2007).
  2. Guebre-Egziabher et al. Nutritional intervention to reduce the n-6/n-3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy humans. Eur J Clin Nutr 62:1287-93 (2008).
  3. Fernandez-Real et al. Circulating adiponectin and plasma fatty acid profile. Clin Chem 51(3):603-9 (2005).
  4. Pischon et al. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 291(14):1730-7 (2004).
  5. Ajuwon and Spurlock. Adiponectin inhibits LPS-stimulated NF-kappaB and IL-6 production and increases PPARgamma2 expression in adipocytes. Am J Physiol Regul Integr Comp Physiol 288:R1220-25 (2005).
  6. Ohashi et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension 47:1108-16 (2006).
  7. Dzielinska et al. Decreased plasma concentration of a novel anti-inflammatory protein—adiponectin—in hypertensive men with coronary artery disease. Thromb Res 110:365-9 (2003).
  8. Shimabukuro et al. Hypoadiponectinemia is closely linked to endothelial dysfunction in man. J Clin Endocrinol Metab 88(7):3236-40 (2003).
  9. Atzmon et al. Adiponectin levels and genotype: a potential regulator of life span in humans. J Gerontol A Biol Sci Med Sci 63A(5):447-53 (2008).
  10. Pischon et al. Association between dietary factors and plasma adiponectin concentrations in men. Am J Clin Nutr 81:780-6 (2005).
  11. Folco et al. Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10. J Biol Chem 284(38):25569-75 (2009).
  12. Otabe et al. Overexpression of human adiponectin in transgenic mice results in suppression of fat accumulation and prevention of premature death by high-calorie diet. Am J Physiol Endocrinol Metab 293:E210-8 (2007).
  13. Shimada et al. Oolong tea increases plasma adiponectin levels and low-density lipoprotein particle size in patients with coronary artery disease. Diabetes Res Clin Pract 65:227-34 (2004).

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