Proanthocyanidins potentiate hypothalamic leptin/STAT3 signalling and Pomc gene expression in rats with diet-induced obesity

Abstract

Objective:Dietary obesity is usually linked with hypothalamic leptin resistance, in which the primary impact is an interference in the homeostatic control of body weight and appetite. Notably, proanthocyanidins (PACs), which are the most abundant phenolic compounds present in human diet, modulate adiposity and food intake. The aim of this study was to assess whether PACs could re-establish appropriate leptin signalling in both the hypothalamus and peripheral tissues.Design:Male Wistar rats were fed either a standard chow diet (STD group, n=7) or a cafeteria diet (CD) for 13 weeks. The CD-fed rats were treated with either grape-seed PAC extract (GSPE) at 25 mg per kg of body weight per day (CD+GSPE group, n=7) or with the vehicle (CD group, n=7) for the last 21 days of the study period. Specific markers for intracellular leptin signalling, inflammation and endoplasmic reticulum stress in the hypothalamus, liver, mesenteric white adipose tissue and skeletal muscle were analysed using immunoblotting and quantitative PCR.Results:GSPE treatment significantly reduced the food intake but did not reverse the hyperleptinemia and body wt gain assessed. However, the animals treated with GSPE exhibited greater hypothalamic activation of signal transducer and activator of transcription-3, which was associated with a rise in the Pomc mRNA levels compared with the CD group. In addition, this restoration of leptin responsiveness was accompanied by lower local inflammation and increased Sirt1 gene expression. The effects of the GSPE treatment in the peripheral tissues were not as evident as those in the hypothalamus, although the GSPE treatment significantly restored the mRNA levels of Socs3 and Ptp1b in the skeletal muscle.Conclusions:The use of GSPE reduces hyperphagia and improves the central and peripheral leptin resistance associated with diet-induced obesity. Our results suggest that GSPE could exert these effects partially by increasing Sirt1 expression and preventing hypothalamic inflammation.

Proanthocyanidin trimer gallate modulates lipid deposition and fatty acid desaturation inCaenorhabditis elegans

“…In comparison, the grape (Vitis vinifera) provides a more diverse source of OPCs, owing to the abundance of galloylated oligomers and type-A linked species (29). Until very recently, studies investigating the effectiveness of OPCs have typically applied the raw extract rather than the purified forms (9). The knowledge base surrounding OPCs mechanistic action is therefore modest and calls for expansion.…”

“…Complex hydroxylation patterns, esterification, glycosylation, and multivariate stereoisomer formations of OPCs result in a wide range of bioactivities specific to individual moieties. A consequence of this complexity is that their separation is exceptionally challenging and thus, even to date, studies have used crude proanthocyanidin mixtures that have led to inconsistent, sometimes conflicting, conclusions (6)(7)(8)(9). It is therefore important to understand the health potential of homogenous OPCs before the synergetic therapeutic effect of OPCs, as demonstrated by TCM, Ayurveda, and European phytotherapies, can be fully understood.…”

Effects of Grape Seed Proanthocyanidin Extract on Obesity

“…Sisley et al [95] have also shown that neuronal GLP-1 receptors mediate the anorexia effect of liraglutide (a persistent GLP-1 agonist). At the same time, GLP-1 activated POMC/CART neurons in the hypothalamus [96], indirectly inhibited neuropeptide Y/agouti-related peptide neurons through β-aminobutyric acid transmission, and together produced signals to reduce food intake, which indicated that GSPE affected the hypothalamic center [97], and then controlled food intake. However, the inhibiting effect of GSPE on food intake needs to be exerted at a specific dose without external pressure and calmness.…”

Ginsenosides reduce body weight and ameliorate hepatic steatosis in high fat diet‑induced obese mice via endoplasmic reticulum stress and p‑STAT3/STAT3 signaling

“…Previously, an increasing number of studies have demonstrated that leptin resistance was a major cause of obesity (65-67). The important reasons are the regulation of p-STaT3 and increased erS in the hypothalamus (68,69).…”

“…For example, liu et al (72) reported that celastrol suppresses appetite, reduces body weight and ameliorates disorders of glucose and lipid metabolism through p-STaT3. ibars et al (68) reported that proanthocyanidins reduce appetite and weight by increasing phosphorylated STaT3. interestingly, the present study produced opposing results in vivo and in vitro.…”