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      Exercise Induced Adipokine Changes and the Metabolic Syndrome

      review-article
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      Journal of Diabetes Research
      Hindawi Publishing Corporation

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          Abstract

          The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF- α , and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

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          Most cited references162

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          Banting lecture 1988. Role of insulin resistance in human disease.

          G M Reaven (1988)
          Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in approximately 25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the beta-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration. Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulin-stimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one.(ABSTRACT TRUNCATED AT 400 WORDS)
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            Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions.

            Adiponectin plays a central role as an antidiabetic and antiatherogenic adipokine. AdipoR1 and AdipoR2 serve as receptors for adiponectin in vitro, and their reduction in obesity seems to be correlated with reduced adiponectin sensitivity. Here we show that adenovirus-mediated expression of AdipoR1 and R2 in the liver of Lepr(-/-) mice increased AMP-activated protein kinase (AMPK) activation and peroxisome proliferator-activated receptor (PPAR)-alpha signaling pathways, respectively. Activation of AMPK reduced gluconeogenesis, whereas expression of the receptors in both cases increased fatty acid oxidation and lead to an amelioration of diabetes. Alternatively, targeted disruption of AdipoR1 resulted in the abrogation of adiponectin-induced AMPK activation, whereas that of AdipoR2 resulted in decreased activity of PPAR-alpha signaling pathways. Simultaneous disruption of both AdipoR1 and R2 abolished adiponectin binding and actions, resulting in increased tissue triglyceride content, inflammation and oxidative stress, and thus leading to insulin resistance and marked glucose intolerance. Therefore, AdipoR1 and R2 serve as the predominant receptors for adiponectin in vivo and play important roles in the regulation of glucose and lipid metabolism, inflammation and oxidative stress in vivo.
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              Metabolic syndrome and risk of cardiovascular disease: a meta-analysis.

              The use of different definitions of the metabolic syndrome has led to inconsistent results on the association between the metabolic syndrome and risk of cardiovascular disease. We examined the association between the metabolic syndrome and risk of cardiovascular disease. A MEDLINE search (1966-April 2005) was conducted to identify prospective studies that examined the association between the metabolic syndrome and risk of cardiovascular disease. Information on sample size, participant characteristics, metabolic syndrome definition, follow-up duration, and endpoint assessment was abstracted. Data from 21 studies met the inclusion criteria and were included. Individuals with the metabolic syndrome, compared to those without, had an increased mortality from all causes (relative risk [RR] 1.35; 95% confidence interval [CI], 1.17-1.56) and cardiovascular disease (RR 1.74; 95% CI, 1.29-2.35); as well as an increased incidence of cardiovascular disease (RR 1.53; 95% CI, 1.26-1.87), coronary heart disease (RR 1.52; 95% CI, 1.37-1.69) and stroke (RR 1.76; 95% CI, 1.37-2.25). The relative risk of cardiovascular disease associated with the metabolic syndrome was higher in women compared with men and higher in studies that used the World Health Organization definition compared with studies that used the Adult Treatment Panel III definition. This analysis strongly suggests that the metabolic syndrome is an important risk factor for cardiovascular disease incidence and mortality, as well as all-cause mortality. The detection, prevention, and treatment of the underlying risk factors of the metabolic syndrome should become an important approach for the reduction of the cardiovascular disease burden in the general population.
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                Author and article information

                Journal
                J Diabetes Res
                J Diabetes Res
                JDR
                Journal of Diabetes Research
                Hindawi Publishing Corporation
                2314-6745
                2314-6753
                2014
                19 January 2014
                : 2014
                : 726861
                Affiliations
                Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3
                Author notes

                Academic Editor: Caroline J. Magri

                Author information
                http://orcid.org/0000-0002-3917-4417
                Article
                10.1155/2014/726861
                3915640
                24563869
                b3eecd2d-6369-4a76-b793-f67fb0e0611b
                Copyright © 2014 S. Golbidi and I. Laher.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 July 2013
                : 18 October 2013
                Categories
                Review Article

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