Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects

Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications (AU)

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Limited beneficial effects of piceatannol supplementation on obesity complications in the obese Zucker rat: gut microbiota, metabolic, endocrine, and cardiac aspects.

Resveratrol is beneficial in obese and diabetic rodents. However, its low bioavailability raises questions about its therapeutic relevance for treating or preventing obesity complications. In this context, many related natural polyphenols are being tested for their putative antidiabetic and anti-obesity effects. This prompted us to study the influence of piceatannol, a polyhydroxylated stilbene, on the prevention of obesity complications in Zucker obese rats. A 6-week supplementation was followed by the determination of various markers in plasma, liver, adipose tissue and heart, together with a large-scale analysis of gut microbiota composition. When given in doses of 15 or 45 mg/kg body weight/day, piceatannol did not reduce either hyperphagia or fat accumulation. It did not modify the profusion of the most abundant phyla in gut, though slight changes were observed in the abundance of several Lactobacillus, Clostridium, and Bacteroides species belonging to Firmicutes and Bacteroidetes. This was accompanied by a tendency to reduce plasma lipopolysaccharides by 30 %, and by a decrease of circulating non-esterified fatty acids, LDL-cholesterol, and lactate. While piceatannol tended to improve lipid handling, it did not mitigate hyperinsulinemia and cardiac hypertrophy. However, it increased cardiac expression of ephrin-B1, a membrane protein that contributes to maintaining cardiomyocyte architecture. Lastly, ascorbyl radical plasma levels and hydrogen peroxide release by adipose tissue were similar in control and treated groups. Thus, piceatannol did not exhibit strong slimming capacities but did limit several obesity complications.

Several statins increase body and liver fat accumulation in a model of metabolic syndrome.

Statins are a family of drugs used in hypercholesterolemia. The aim of this study was to analyze the effect of statins on body and liver fat accumulation in obese Zucker rats. Seventy Zucker (fa/fa) rats were divided into seven groups. Rats from six statin groups were treated with pravastatin, simvastatin, atorvastatin, rosuvastatin, fluvastatin and lovastatin respectively, at a dose of 0.6 mg/kg body weight/day. After 6 weeks, liver and white adipose tissue from intra-abdominal and subcutaneous locations were dissected and weighed. Subcutaneous adipose tissue from rosuvastatin, atorvastatin, fluvastatin and lovastatin treated rats was significantly increased. Fatty acid synthase (FAS) activity was increased by the administration of fluvastatin and lovastatin, as was glucose-6-P dehydrogenase (G6PDH) by the administration of atorvastatin and lovastatin. No changes were observed in malic enzyme (ME) activity. Furthermore, heparin-releasable lipoprotein lipase (HR-LPL) was increased in all groups where the subcutaneous depot was increased, and total LPL increased only in rosuvastatin and fluvastatin-treated groups. With regard to liver, there were no changes in weight but the amount of triacylglycerols was increased in rosuvastatin group, as well as its liver damage was higher. In this group FAS and G6PDH activities were increased and no changes were observed in ME, acyl CoA oxidase (ACO) and carnitine palmitoyltransferase-1a (CPT-1a) activities. All statins, with the exception of simvastatin, worsen insulin resistance. These results show that statins have different effects on body fat accumulation. Moreover, rosuvastatin also shows a prosteatotic effect. These results should be taken into account for statin choice in prescription.

Resveratrol attenuates steatosis in obese Zucker rats by decreasing fatty acid availability and reducing oxidative stress.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common manifestations of chronic liver disease worldwide. The aim of the present study was to assess the effect of resveratrol on liver fat accumulation, as well as on the activity of those enzymes involved in lipogenesis and fatty acid oxidation in fa/fa Zucker rats. A total of thirty rats were assigned to three experimental groups and orally treated with resveratrol for 6 weeks, or without resveratrol (C: control group; RSV15 group: 15 mg/kg body weight per d; RSV45 group: 45 mg/kg body weight per d). Liver histological analysis was performed by microscopy. Levels of hepatic carnitine palmitoyltransferase-Ia (CPT-Ia), acyl-coenzyme A oxidase (ACO), fatty acid synthase, glucose-6-phosphate dehydrogenase and malic enzyme were assessed by spectrophotometry, and acetyl-CoA carboxylase was assessed by radiometry. Commercial kits were used to determine serum TAG, NEFA, total HDL and non-HDL-cholesterol, glycerol, ketonic bodies, glucose, insulin, adiponectin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), hepatic TAG, thiobarbituric acid reactive substrates, GSH (GSSG) and superoxide dismutase. Resveratrol reduced liver weight and TAG content. It did not modify the activity of lipogenic enzymes but it did increase CPT-Ia and ACO activities. NEFA and ALP were reduced in both resveratrol-treated groups. AST/GOT was reduced only by the lowest dose. ALT/GPT, TAG and adiponectin remained unchanged. Resveratrol reduced liver oxidative stress. This study demonstrates that resveratrol can protect the liver from NAFLD by reducing fatty acid availability. Moreover, resveratrol also protects liver from oxidative stress.

Adaptación en el intestino corto: efecto de la nutrición enteral mínima y los probióticos sobre la proliferación y la apoptosis en la pared intestinal / Adaptation in the small intestine: effect of minimal enteral nutrition and probiotics on proliferation and apoptosis in the intestinal wall

Introducción. La integridad de la pared intestinal es fundamental en la función de la barrera y depende del balance de proliferación/apoptosis. El intestino Corto (IC) o la Nutrición Parenteral (NP) inducen un alto índice de translocación bacteriana (TB) seguramente por fallo dela barrera intestinal. La administración de probióticos o la nutrición enteral mínima(NEM) han reducido la TB en modelos animales. Objetivos. Determinar en 2 modelos animales de TB (IC o NP)el efecto de la NEM y los probióticos sobre los índices de proliferación(IP) y apoptosis (IA) de la pared intestinal. Metodología. Setenta y una ratas Wistar, divididas en 4 grupos: 1)NP (N=23): Nutrición parenteral; 2) NPNEM (N=16): NP + NEM (2,9g/100 g/día dieta estándar); 3) RES (N=15): Resección intestinal 80%y dieta oral estándar; 4) RESPROB (N=17): RES + probióticos (..) (AU)

Background. The intestinal wall integrity is central to the barrier function and depends on the balance of proliferation/apoptosis. Short bowel (SB) or Parenteral Nutrition (PN) induce high bacterial translocation (BT) probably by the intestinal barrier bug. Probiotics or minimal enteral nutrition (MEN) have reduced BT in animal models. Objective. Determine in two BT animal models (SB or PN) the effect of MEN or probiotics on proliferation and apoptosis rates of the intestinal wall. Methods. Seventy-one Wistar rats, divided into 4 groups: 1) PN(N = 23): parenteral nutrition; 2) PNMEN (N = 16): PN + MEN (2.9g/100 g/day standard diet); 3) RES (N = 15): 80% bowel resection (..) (AU)

[Adaptation in the small intestine: Effect of minimal enteral nutrition and probiotics on proliferation and apoptosis in the intestinal wall]. / Adaptación en el intestino corto: efecto de la nutrición enteral mínima y los probióticos sobre la proliferación y la apoptosis en la pared intestinal.

BACKGROUND: The intestinal wall integrity is central to the barrier function and depends on the balance of proliferation/apoptosis. Short bowel (SB) or Parenteral Nutrition (PN) induce high bacterial translocation (BT) probably by the intestinal barrier bug. Probiotics or minimal enteral nutrition (MEN) have reduced BT in animal models. OBJECTIVE: Determine in two BT animal models (SB or PN) the effect of MEN or probiotics on proliferation and apoptosis rates of the intestinal wall. METHODS: Seventy-one Wistar rats, divided into 4 groups: 1) PN (N = 23): parenteral nutrition; 2) PNMEN (N = 16): PN + MEN (2.9 g/100 g/day standard diet); 3) RES (N = 15): 80% bowel resection and standard oral diet; 4) RESPROB (N = 17): RES + probiotics (7 X 10(9) CFU Bifidobacterium lactis). After 10 days in metabolic cages, mesenteryc lymph nodes, portal blood and peripheral blood were cultured. By immunohistochemistry, proliferation and apoptosis index were calculated as well as the proliferation-apoptosis rate. RESULTS: BT: decreased in PNMEN (45%) and RESPROB groups (35%) versus PN (65%) and RES (67%) groups (p<0.05). Proliferation index: was better in PNMEN (12,07) and RESPROB (13,93) groups than PN (7,45) and RES (5,54) groups. (p