Role of Adiponectin in the Metabolic Syndrome: Current Perspectives on its Modulation as a Treatment Strategy

Abstract

Adiponectin, a secretory protein specifically expressed by adipose tissue, has been shown to play a critical role in the maintenance of metabolic homeostasis. A deficiency of adiponectin has been linked to a wide variety of metabolic abnormalities, including obesity and associated disorders such as insulin resistance, hyperglycemia, dyslipidemia, hypertension and nonalcoholic fatty liver disease, collectively referred to as the "metabolic syndrome". Conversely, increased expression of adiponectin corrects these abnormalities, as revealed by the positive metabolic effects observed in genetic over expression studies or by administration of recombinant adiponectin. This has led to widespread interest in its role as a therapeutic target for treatment of a range of metabolic disorders such as diabetes mellitus, obesity, inflammatory and cardiovascular diseases. Various therapeutic approaches targeted at increasing adiponectin levels, or its activity, are being explored. These consist of increasing expression of adiponectin or its receptors by inducers, increasing circulating levels of adiponectin by administering recombinant protein, peptide mimetic approaches, or increasing expression/activity of its downstream effectors such as AMPK or PPAR alpha. Many of these approaches have achieved therapeutic benefits in animal models of metabolic diseases. Despite the profusion of research on adiponectin and ways to modulate it, there are limited number of studies focused on smallmolecule based-therapeutic approaches. In this review, we summarize what is currently known with respect to the therapeutic potential of adiponectin and discuss the challenges in designing small molecule-based therapies.

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

“…The risk of insulin resistance at follow-up was higher in those patients with high levels of irisin and leptin. Although adiponectin has been demonstrated to have an insulin-sensitizing activity [47], no association was observed between the insulin resistance during the weight maintenance period and adiponectin levels. In fact, only high irisin plasma levels at baseline were able to predict the classification of patients as insulin resistant during the weight maintenance period, independent of gender, body weight at followup and insulin sensitivity state at baseline and even when the change in fat mass from the end of the dietary treatment to follow-up was included as a confounder factor.…”

“…Adiponectin is considered an insulin sensitizer, has antidiabetic properties and decreased adiponectin levels are associated with obesity and insulin resistance [47]. Leptin collaborates with insulin to regulate glucose and lipid metabolism, in addition to regulating food intake and metabolic rate via the central nervous system [48].…”

Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance

“…FSL are also known to be deficient in leptin and adiponectin, and adiponectin is related to some symptoms of depression in humans (33). Previous studies have associated a hyperactivity of the HPA axis with haploinsufficiency in adiponectin (34), which stimulates fattyacid oxidation (35), whose metabolism seems to be impaired in only nrFSL based on alterations in Cyb5r2-and Elovl7-mediated regulation of fatty-acid elongation. Therefore, our results suggest that adiponectin (33) may be relevant in determining occurrence of resistance to antidepressant treatment, and this is an interesting topic for future investigation.…”

Mice lacking have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease

“…These individuals are considered leptin resistant (47). Obesity has also been associated with reduced adiponectin secretion (48). Our Arv1 -/ -animals secreted more adiponectin per gram of fat mass and had a higher adiponectin: leptin ratio (~9:1) then WT animals.…”