Medico

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Journal of Nutritional Biochemistry 20 (2009) 831 – 839

REVIEWS: CURRENT TOPICS

Adiponectin and energy homeostasis: consensus and controversy
Sami Dridia,⁎, Mohammed Taouisb
a

Department of Ophthalmology & Visual Sciences, Ocular Angiogenesis Research Laboratory, University of Kentucky, Lexington, KY 40506, USA b NOPA, UMR 1197, UniversityParis sud, bat 447, 91405 Orsay Cedex, France Received 12 February 2009; received in revised form 27 April 2009; accepted 2 June 2009

Abstract Adiponectin regulates energy homeostasis through the modulation of glucose and fatty acid metabolism in peripheral tissues. However, its central effect on energy balance remains unclear and controversial. Despite the disparate data, recent advances in ourunderstanding of the signal transduction mechanisms used by adiponectin in the periphery and in the hypothalamus suggest that intracellular cross-talk between adiponectin, leptin and insulin may occur at several levels. The present review will summarize recent reports describing the peripheral and central effects of adiponectin and discuss progress concerning its molecular mechanisms. We willalso particularly focus on apparent controversies and related mechanisms associated with the central effects of adiponectin on energy homeostasis. © 2009 Elsevier Inc. All rights reserved.
Keywords: Adiponectin; Energy homeostasis; Periphery; Hypothalamus

1. Introduction Obesity currently qualifies as a worldwide health epidemic [1,2]. It is associated with increased risk of diabetes,cardiovascular disease, obstructive sleep apnea, nonalcoholic fatty liver disease, malignancies, gall bladder disease, arthritis and various complications [1]. It also increases mortality [3]. Obesity is fundamentally a problem of energy balance in that self-evidently it can develop when

Abbreviations: ACC, acetyl-coenzyme-A carboxylase; ACO, Acylcoenzyme A oxidase; Adip-R1/Adip-R2, adiponectin receptor1/2; Acrp30, adipocyte complement related protein30; AGRP, agouti related protein; Akt, protein kinase B; AMPK, adenosine monophosphate-activated protein kinase; APPL1, Adaptor protein containing PH domain, PTB domain and leucine zipper motif; ARC, arcuate nucleus; CART, cocaine- and amphetamine-regulated transcript; CD36, cluster of differentiation 36; CSF, cerebrospinal fluid; CRH, corticotropinreleasing hormone; FOXO1, forkhead transcription factor 1; GFP, green fluorescent protein; JAK2, janus kinase 2; LHA, lateral hypothalamus; MAPK, mitogen activated protein kinase; NPY, neuropeptide Y; PA, area postrema; POMC, pro-opiomelanocortin; PPARα, peroxisome proliferator-activated receptor α; PVN, paraventricular nucleus; STAT3, signal transducer and activator of transcription 3; TRH,thyrotropin releasing hormone; VMH, ventromedial nucleus of the hypothalamus. ⁎ Corresponding author. Tel.: +1 859 257 3902; fax: +1 859 257 2317. E-mail address: sami.dridi@uky.edu (S. Dridi). 0955-2863/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.jnutbio.2009.06.003

energy intake exceeds energy expenditure, resulting in fat accumulation and excessive adipose tissuemass. Adipose tissue, in addition to its function as the major storage depot for triglycerides, is an active endocrine tissue sensing metabolic signals and secreting hormones called adipocytokines/adipokines that affect whole-body energy homeostasis [4–6]. The list of adipocytokines keeps growing [7,8]. Adiponectin is the most abundant adipocytokine [9]. Unlike leptin and other adiposetissue-derived hormones which circulate at picograms or nanograms per milliliter, adiponectin circulates at very high levels (micrograms per milliliter). It circulates as several multimeric species, including a highmolecular-weight (HMW) form thought to be the most clinically relevant. Adiponectin is decreased in obesity, is inversely related to glucose and insulin and increases during fasting [9]....