Associations of Serum Adiponectin with Skeletal Muscle Morphology and Insulin Sensitivity

Ingelsson, Erik; Ärnlöv, Johan; Zethelius, Björn; Vasan, Ramachandran S.; Flyvbjerg, Allan; Frystyk, Jan; Berne, Christian; Hänni, Arvo; Lind, Lars; Sundström, Johan

doi:10.1210/jc.2008-1772

Cited by 23 publications

(20 citation statements)

References 21 publications

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“…It is known that exogenously delivered adiponectin has similar effects on skeletal muscle that we observed in our CA-PPAR␥ animals, including activation of AMPK and ACC, reduced myocellular triglyceride content, altered fiber-type composition, increased expression of genes involved in lipid oxidation and mitochondrial function, and improved insulin sensitivity (21,37). Our model suggests that myocyte-produced adiponectin could provide an additional source of adiponectin signaling additive to the effect of circulating hormone.…”

Section: Discussionsupporting

confidence: 70%

Selective activation of PPARγ in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance

Amin

Mathews

Camp

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

105

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Amin RH, Mathews ST., Camp HS, Ding L, Leff T. Selective activation of PPAR␥ in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance. Am J Physiol Endocrinol Metab 298: E28 -E37, 2010. First published October 20, 2009 doi:10.1152/ajpendo.00446.2009.-The nuclear receptor peroxisome proliferator-activated receptor (PPAR)␥ plays a key role in regulating whole body glucose homeostasis and insulin sensitivity. Although it is expressed most highly in adipose, it is also present at lower levels in many tissues, including skeletal muscle. The role muscle PPAR␥ plays in metabolic regulation and in mediating the antidiabetic effects of the thiazolidinediones is not understood. The goal of this work was to examine the molecular and physiological effects of PPAR␥ activation in muscle cells. We found that pharmacological activation of PPAR␥ in primary cultured myocytes, and genetic activation of muscle PPAR␥ in muscle tissue of transgenic mice, induced the production of adiponectin directly from muscle cells. This muscle-produced adiponectin was functional and capable of stimulating adiponectin signaling in myocytes. In addition, elevated skeletal muscle PPAR␥ activity in transgenic mice provided a significant protection from high-fat diet-induced insulin resistance and associated changes in muscle phenotype, including reduced myocyte lipid content and an increase in the proportion of oxidative muscle fiber types. Our findings demonstrate that PPAR␥ activation in skeletal muscle can have a significant protective effect on whole body glucose homeostasis and insulin resistance and that myocytes can produce and secrete functional adiponectin in a PPAR␥-dependent manner. We propose that activation of PPAR␥ in myocytes induces a local production of adiponectin that acts on muscle tissue to improve insulin sensitivity. diabetes; peroxisome proliferator-activated receptor-␥; adiponectin; skeletal muscle; transgenic mice ACTIVATION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-␥ (PPAR␥) by thiazolidinedione (TZD) treatment causes profound metabolic changes that lead to improvements in whole body insulin sensitivity and glucose homeostasis in diabetic individuals (9,17,23,32). Although one of the major metabolic effects of PPAR␥ activation is to improve skeletal muscle insulin sensitivity, the degree to which these effects are mediated by PPAR␥ resident in muscle tissue is not clearly understood. The level of PPAR␥ in muscle is relatively low compared with adipose tissue (3, 26), and many of the known effects of TZDs on muscle could potentially be the indirect result of PPAR␥ activation in adipose tissue (35). However, several lines of evidence indicate a specific metabolic role for muscle PPAR␥, suggesting that it contributes directly to the antidiabetic effects of the TZDs.The strongest suggestion of a direct metabolic role for muscle PPAR␥ comes from a study using a muscle-specific PPAR␥ knockout line. Hevener et al. (19) found that mice without skeletal muscle PPAR␥...

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Section: Discussionsupporting

confidence: 70%

Selective activation of PPARγ in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance

Amin

Mathews

Camp

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

105

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“…In contrast to results obtained with rodent muscle, similar AdipoR1 and AdipoR2 expression was observed in isolated muscle strips of type 2 diabetic and nondiabetic men [165]. A recent human study [166] revealed that circulating adiponectin concentrations were higher with increasing skeletal muscle capillary density and in individuals with higher proportions of slow oxidative muscle fibers, and that adiponectin could be a partial mediator of the relationship between skeletal muscle morphology and insulin sensitivity.…”

Section: Skeletal Musclementioning

confidence: 58%

Adiponectin action from head to toe

Brochu-Gaudreau

Rehfeldt

Blouin

et al. 2009

Endocr

280

247

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Adiponectin, the most abundant protein secreted by white adipose tissue, is known for its involvement in obesity-related disorders such as insulin resistance, type 2 diabetes mellitus and atherosclerosis. Moreover, modulation of the circulating adiponectin concentration is observed in pathologies that are more or less obesity-related, such as cancer and rheumatoid arthritis. The wide distribution of adiponectin receptors in various organs and tissues suggests that adiponectin has pleiotropic effects on numerous physiological processes. Besides its well-known insulin-sensitizing, anti-inflammatory and antiatherosclerotic properties, accumulating evidence suggests that adiponectin may also have anticancer properties and be cardioprotective. A beneficial effect of adiponectin on female reproductive function was also suggested. Since adiponectin has numerous beneficial biological functions, its use as a therapeutic agent has been suggested. However, the use of adiponectin or its receptors as therapeutic targets is complicated by the presence of different adiponectin oligomeric isoforms and production sites, by multiple receptors with differing affinities for adiponectin isoforms, and by cell-type-specific effects in different tissues. In this review, we discuss the known and potential roles of adiponectin in various tissues and pathologies. The therapeutic promise of administration of adiponectin and the use of its circulating levels as a diagnostic biomarker are further discussed based on the latest experimental studies.

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“…More specifically, obese diabetic rats have only low oxidative type I fibers, whereas rats with hypertension or hyperlipidemia have both high oxidative type IIA and type IIC and low oxidative type I fibers in their skeletal muscles. The proportion of muscle fibers, as well as the capillary density in skeletal muscles is positively correlated with the levels of the circulating adiponectin, a hormone associated with insulin resistance and type II diabetes [25]. These studies showed that changes in the muscle fiber profile can result from metabolic abnormalities.…”

Section: Discussionmentioning

confidence: 86%

Can Chronic Intra-Abdominal Hypertension Cause Oxidative Stress to the Abdominal Wall Muscles? An Experimental Study

Kotidis

Papavramidis

Ioannidis

et al. 2012

Journal of Surgical Research

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Associations of Serum Adiponectin with Skeletal Muscle Morphology and Insulin Sensitivity

Cited by 23 publications

References 21 publications

Selective activation of PPARγ in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance

Selective activation of PPARγ in skeletal muscle induces endogenous production of adiponectin and protects mice from diet-induced insulin resistance

Adiponectin action from head to toe

Can Chronic Intra-Abdominal Hypertension Cause Oxidative Stress to the Abdominal Wall Muscles? An Experimental Study

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