Adipose tissue releases bioactive mediators called adipokines. This review focuses on the effects of omentin, vaspin, cardiotrophin-1, Tumor necrosis factor-like Weak Inducer of Apoptosis (TWEAK) and nephroblastoma overexpressed (NOV/CCN3) on obesity and diabetes. Omentin is produced by the stromal-vascular fraction of visceral adipose tissue. Obesity reduces omentin serum concentrations and adipose tissue secretion in adults and adolescents. This adipokine regulates insulin sensitivity, but its clinical relevance has to be confirmed. Vaspin is produced by visceral and subcutaneous adipose tissues. Vaspin levels are higher in obese subjects, as well as in subjects showing insulin resistance or type 2 diabetes. Cardiotrophin-1 is an adipokine with a similar structure as cytokines from interleukin-6 family. There is some controversy regarding the regulation of cardiotrophin-1 levels in obese -subjects, but gene expression levels of cardiotrophin-1 are down-regulated in white adipose tissue from diet-induced obese mice. It also shows anti-obesity and hypoglycemic properties. TWEAK is a potential regulator of the low-grade chronic inflammation characteristic of obesity. TWEAK levels seem not to be directly related to adiposity, and metabolic factors play a critical role in its regulation. Finally, a strong correlation has been found between plasma NOV/CCN3 concentration and fat mass. This adipokine improves insulin actions.

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Phenolic compounds might modulate adiposity. Here, we report our observation that polyphenols and phenolic acids inhibit adipogenesis in 3T3-L1 with different intensity depending on the family and the stage of differentiation. While quercetin and resveratrol inhibited lipid accumulation along the whole process of differentiation, apigenin and myricetin were active during the early and latest stages, but not intermediate, contrary to hesperidin. The activity of phenolic acids was limited to the early stages of the differentiation process, except p-coumaric and ellagic acids. This anti-adipogenic effect was accompanied by down-regulation of Scd1 and Lpl. Molecular docking analysis revealed that the inhibitory activity of these phenolic compounds over the early stages of adipogenesis exhibits a significant correlation (r = 0.7034; p = 0.005) with their binding affinity to the ligand-binding domain of PPARγ. Results show that polyphenols and phenolic acids would interact with specific residues of the receptor, which could determine their potential anti-adipogenic activity during the early stages of the differentiation. Residues Phe264, His266, Ile281, Cys285 and Met348 are the most frequently involved in these interactions, which might suggest a crucial role for these amino acids modulating the activity of the receptor. These data contribute to elucidate the possible mechanisms of phenolic compounds in the control of adipogenesis.

Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (p-coumaric, ellagic, ferulic, gallic, and vanillic acids) regulating C. elegans fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress, and aging, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPRER), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in C. elegans through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, aging, and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders.

This article is available online at http://www.jlr.org effects by interacting with the glycoprotein 130 (gp130)/ leukemia inhibitory factor receptor heterodimer ( 1 ). Adipose tissue has been identifi ed as a source of CT-1 ( 2 ), and this cytokine is capable of activating major signaling pathways involved in metabolic control in adipocytes ( 3 ). Moreover, it has been reported that CT-1 levels are raised in obesity and metabolic syndrome ( 2 ), suggesting that CT-1 could be a new marker for obesity and related diseases. A recent study by our group has revealed that CT-1 is a key regulator of energy homeostasis, as well as of glucose and lipid metabolism ( 4 ). Thus, chronic recombinant CT-1 (rCT-1) treatment reduced body weight and corrected insulin resistance in ob/ob and high-fat-fed obese mice by reducing food intake and enhancing energy expenditure. Moreover, rCT-1 induced dramatic white adipose tissue remodeling characterized by the upregulation of genes implicated in the control of fatty acid oxidation, mitochondrial biogenesis, and lipolysis. In this context, it has been reported that adipocytes from rCT-1-treated mice exhibited an increased lipolytic response to isoproterenol, while adipocytes from old obese CT-1 -null mice responded poorly to isoproterenol, suggesting that CT-1 might play a role in the regulation of lipolysis ( 4 ). However, the mechanism underlying the lipolytic action of CT-1 still remains unknown.During lipolysis, intracellular triacylglycerol (TAG) is hydrolyzed through the consecutive action of three major lipases: adipose triglyceride lipase (ATGL/desnutrin), Abbreviations: AdPLA , adipocyte phospholipase A2; AICAR, aminoimidazole carboxamide ribonucleotide; ATGL, adipose triglyceride lipase (desnutrin); CGI-58, comparative gene identifi cation-58; cGMP, cyclic guanosine monophosphate; CT-1, cardiotrophin-1; DAG, diacylglycerol; Gi, inhibitory guanine nucleotide binding protein; gp130, glycoprotein 130; Gs, stimulatory guanine nucleotide binding protein; G0S2, G0/G1 switch gene 2; HPTLC, high-performance TLC; HSL, hormone sensitive lipase; IL, interleukin; MAG, monoacylglycerol; PDE3B, phosphodiesterase 3B; PK, protein kinase; rCT-1, recombinant cardiotrophin-1; TAG, triacylglycerol. 1 M. Bustos and M. J. Moreno-Aliaga contributed equally to the work.