Resveratrol supplementation improves white adipose tissue function in a depot-specific manner in Zucker diabetic fatty rats

Abstract

Resveratrol (RSV) is a polyphenolic compound suggested to have anti-diabetic properties. Surprisingly, little is known regarding the effects of RSV supplementation on adipose tissue (AT) metabolism in vivo. The purpose of this study was to assess the effects of RSV on mitochondrial content and respiration, glyceroneogenesis (GNG), and adiponectin secretion in adipose tissue from Zucker diabetic fatty (ZDF) rats. Five-week-old ZDF rats were fed a chow diet with (ZDF RSV) or without (ZDF chow) RSV (200 mg/kg body wt) for 6 wk. Changes in adipose tissue metabolism were assessed in subcutaneous (scAT) and intra-abdominal [retroperitoneal (rpWAT), epididymal (eWAT)] adipose tissue depots. ZDF RSV rats showed lower fasting glucose and higher circulating adiponectin, as well as lower glucose area under the curve during intraperitoneal glucose and insulin tolerance tests than ZDF chow. [¹⁴C]pyruvate incorporation into triglycerides and adiponectin secretion were higher in scAT from ZDF RSV rats, concurrent with increases in adipose tissue triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and the phosphorylation of pyruvate dehydrogenase-E1α (PDH) (Ser293) protein content in this depot. Moreover, uncoupled mitochondrial respiration and complex I and II-supported respiration were increased in both scAT and rpWAT, which correlated with increases in cytochrome c oxidase subunit IV (COX4) protein content. In vitro treatment of scAT with RSV (50 μmol/l; 24 h) induced pyruvate dehydrogenase kinase 4 (PDK4) and peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) mRNA expression. Collectively, these data demonstrate that RSV can induce adipose tissue mitochondrial biogenesis in parallel with increases in GNG and adiponectin secretion.

Anti-atherogenic properties of resveratrol: 4-week resveratrol administration associated with serum concentrations of SIRT1, adiponectin, S100A8/A9 and VSMCs contractility in a rat model

“…Beaudoin et al (47) demonstrated that 6 weeks of high-dose resveratrol administration (200 mg/kg daily) increases the adiponectin concentration and its release from adipose tissue in Zucker rats. Gómez-Zorita et al (48) demonstrated similar results to Beaudoin et al (47) following 6 weeks of 15 mg/kg resveratrol administration daily. By contrast, Palsamy and Subramanian (49) did not observe a significant increase of plasma adiponectin levels following 30 days of low-dose resveratrol treatment (5 mg/kg) in a healthy population of Wistar rats.…”

Resveratrol treatment rescues hyperleptinemia and improves hypothalamic leptin signaling programmed by maternal high-fat diet in rats

“…It is possible that in our experimental model, resveratrol was able to change the molecular profile of these metabolic pathways resulting in lower fat deposition and improvement of obesity. Contrarily, in a recent study using Zucker diabetic fatty (ZDF) rats, it was demonstrated that resveratrol treatment (200 mg/Kg BW/day) did not affect adipose tissue mass or body weight, but resveratrol induced marked changes in the adipose tissue metabolism, such as increased mitochondrial biogenesis with increase in peroxisome proliferator-activated receptor coactivator-1 (PGC-1α) and also increased adiponectin synthesis in a depot-specific manner [27]. Another possible mechanism associated with reduced fat mass induced by resveratrol would be through the increase in fatty acid oxidation in skeletal muscle and liver, increasing energy expenditure and possibly increasing the demand of lipolysis [28].…”

In adipose tissue, increased mitochondrial emission of reactive oxygen species is important for short-term high-fat diet-induced insulin resistance in mice

“…Adipocyte cell sizing and immunohistochemistry Adipose tissue was fixed, embedded and stained as previously reported [22]. Macrophage infiltration was assessed by F4/80 (1:100, AbD Serotec, BioRad, Hercules, CA, USA) staining visualised using the Vectastain ABC kit (Vector Laboratories, Burlingame, CA, USA).…”

“…High-resolution respirometry Mitochondrial respiration was determined in permeabilised WAT in an Oxygraph high-resolution respirometer chamber at 37°C (Oroboros Instruments, Innsbruck, Austria) as previously described [22,23]. ADP-stimulated respiration (state 3) was measured in the presence of pyruvate (5 mmol/l), malate (5 mmol/l) and ADP (5 mmol/l) or malate (5 mmol/l), L-carnitine (5 mmol/l), palmitoyl-CoA (50 μmol/l) and ADP (5 mmol/l).…”