Adiponectin

Adipowhat?

Dr. Dicken Weatherby and Beth Ellen DiLuglio, MS, RDN, LDN

Adiponectin is a protein-based hormone secreted primarily by adipocytes though it is produced in endothelial cells, skeletal muscle, and cardiac muscle as well. It is found to have beneficial anti-inflammatory, anti-atherogenic, insulin-sensitizing effects.[1]

This complex multifaceted protein improves insulin sensitivity, helps modulate inflammation, and reduces risk of atherosclerosis, cardiovascular disease, metabolic syndrome, and type 2 diabetes. Cardiometabolic disease is associated with low levels of adiponectin.[2] [3] [4]

It exerts its effects in several tissues including blood vessels, bone, brain, immune cells, kidney, liver, and pancreatic beta cells. A reduction in adiponectin has been associated with several metabolic disorders and an inverse correlation is observed in type 2 diabetes, insulin resistance, cardiovascular disease, myocardial infarction, and obesity.[5]

Adiponectin - effects on tissues

Adipose tissue

Increased glucose uptake, fat storage, adipogenesis, decreased inflammation

Beta cells

Increased glucose-stimulated insulin secretion and viability, decreased apoptosis

Endothelium

Increased angiogenesis and function, decreased oxidative stress

Heart

Decreased injury and apoptosis

Kidney

Increased function and recovery, decreased oxidative stress and apoptosis

Liver

Increased insulin sensitivity, decreased gluconeogenesis and lipogenesis

Macrophages

Increased insulin sensitivity, decreased inflammation

Muscle

Increased fatty acid oxidation

 

Adiponectin has favorable effects on metabolism and energy balance, increasing the use of fatty acids for energy and reducing generation of glucose by the liver. Ironically, though levels increase in response to fasting and will increase appetite and food intake, adiponectin levels are inversely correlated with body fat and BMI. Levels tends to be higher in women than men.[6] [7] [8] [9] [10]

Adiponectin is found to improve insulin sensitivity by increasing fat oxidation and glucose uptake in skeletal muscle, and decreasing fat accumulation in muscle, liver, and other tissues. It promotes glucose uptake and fat storage in adipose tissue which also contributes to increased insulin sensitivity.[11]

Interestingly, healthy adipose tissue produces an abundance of adiponectin while inflamed fibrotic adipose tissue produces less, correlating with metabolic disease states.[12]

Higher levels of adiponectin were significantly correlated with reduced risk of developing type 2 diabetes during a 5.8 prospective cohort study of 382 healthy postmenopausal women. Lower levels were associated with increased BMI, fasting blood glucose, triglycerides, and development of type 2 diabetes.[13]

Adiponectin levels may be influenced by diet, exercise habits, genetic factors, body fat distribution, sleep deprivation, smoking, and medications, though some research is conflicting. Researchers suggest that adiponectin may increase as an anti-inflammatory response in chronic disease. Ultimately, researchers conclude that “Adiponectin is an adipokine with anti-inflammatory, antioxidant, antiatherogenic, pro-angiogenic, vasoprotective, and insulin-sensitizing properties.”[14]

Adiponectin increases in response to calorie restriction, weight loss, long-term exercise of 12 weeks or more, and use of nutraceuticals including omega-3 fatty acids, fish oil, DHA,  safflower oil, conjugated linoleic acid (CLA), grapeseed extract, green tea extract, taurine, and resveratrol.[15] [16] Low levels of adiponectin are associated with obesity, abdominal obesity (“apple shape”), diabetes, insulin resistance, metabolic syndrome, atherosclerosis, cardiovascular disease, and smoking.[17] [18] [19]

References

[1] Achari, Arunkumar E, and Sushil K Jain. “Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction.” International journal of molecular sciences vol. 18,6 1321. 21 Jun. 2017, [R]

[2] Maeda, Norikazu et al. “Adiponectin, a unique adipocyte-derived factor beyond hormones.” Atherosclerosis vol. 292 (2020): 1-9. doi:10.1016/j.atherosclerosis.2019.10.021 [R]

[3] Wang, Zhao V, and Philipp E Scherer. “Adiponectin, the past two decades.” Journal of molecular cell biology vol. 8,2 (2016): 93-100.  [R]

[4] Kadowaki, Takashi et al. “The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS.” FEBS letters vol. 582,1 (2008): 74-80. [R]

[5] Straub, Leon G., and Philipp E. Scherer. "Metabolic messengers: adiponectin." Nature Metabolism 1.3 (2019): 334-339. [R]

[6] Mahan, L. Kathleen; Raymond, Janice L. Krause's Food & the Nutrition Care Process (Krause's Food & Nutrition Therapy). Elsevier Health Sciences. Kindle Edition.

[7] Awofala, Awoyemi Abayomi, et al. "Adiponectin and human eating behaviour: a Mendelian randomization study." Egyptian Journal of Medical Human Genetics 20.1 (2019): 17. [R]

[8] Ahima, Rexford S, and Daniel A Antwi. “Brain regulation of appetite and satiety.” Endocrinology and metabolism clinics of North America vol. 37,4 (2008): 811-23.  [R]

[9] Steinberg, Gregory R, and Bruce E Kemp. “Adiponectin: starving for attention.” Cell metabolism vol. 6,1 (2007): 3-4.  [R]

[10] Kadowaki, Takashi et al. “The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS.” FEBS letters vol. 582,1 (2008): 74-80.  [R]

[11] Stern, Jennifer H et al. “Adiponectin, Leptin, and Fatty Acids in the Maintenance of Metabolic Homeostasis through Adipose Tissue Crosstalk.” Cell metabolism vol. 23,5 (2016): 770-84.  [R]

[12] Straub, Leon G., and Philipp E. Scherer. "Metabolic messengers: adiponectin." Nature Metabolism 1.3 (2019): 334-339. [R]

[13] Darabi, Hossein et al. “Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women.” Medicine vol. 94,33 (2015): e1347.  [R]

[14] Katsiki, Niki et al. “Adiponectin, lipids and atherosclerosis.” Current opinion in lipidology vol. 28,4 (2017): 347-354.  [R]

[15] Hui, Xiaoyan et al. “Adiponectin and cardiovascular health: an update.” British journal of pharmacology vol. 165,3 (2012): 574-90.  [R]

[16] Akbarpour M. (2013). The effect of aerobic training on serum adiponectin and leptin levels and inflammatory markers of coronary heart disease in obese men. Biology of sport, 30(1), 21–27. [R]

[17] Blüher, M et al. “Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism.” Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association vol. 113,9 (2005): 534-7.  [R]

[18] Aleidi S, Issa A, Bustanji H, Khalil M, Bustanji Y. Adiponectin serum levels correlate with insulin resistance in type 2 diabetic patients. Saudi Pharm J. 2015;23(3):250-256.  [R]

[19] Abdella, Nabila A, and Olusegun A Mojiminiyi. “Clinical Applications of Adiponectin Measurements in Type 2 Diabetes Mellitus: Screening, Diagnosis, and Marker of Diabetes Control.” Disease markers vol. 2018 5187940. 5 Jul. 2018, [R]

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