Dietary Protein Modulates the Efficacy of Taurine Supplementation on Adaptive Islet Function and Morphology in Obesity.

Adaptation of islet ß-cell mass and function under limiting or excess nutrient availability is critical for maintenance of glucose homeostasis. Taurine regulates islet function of obese mice in normal and low dietary protein conditions, but whether this involves remodeling of the endocrine pancreas architecture is not well understood. Here, we carried functional and morphometric evaluation of the endocrine pancreas of normal and protein-restricted mice fed a high-fat diet (HFD) and investigated the role of taurine supplementation. Weaned mice were placed in a normal (C) or a low-protein diet (R) for 6 weeks, followed by HFD for 8 weeks (CH and RH). Half of HFD groups received 5% taurine supplementation since weaning (CHT and RHT) until the end of the experiment. Isolated islets from both CH and RH groups showed increased insulin release in association with increased pancreas weight and independently of changes in islet or ß-cell area. In normal protein CHT mice, taurine supplementation prevented obesity-induced insulin hypersecretion and promoted increased islet and ß-cell areas in association with increased protein expression of the proliferation marker, PCNA. On a low-protein background, taurine effects on islet function and morphology were blunted, but it prevented obesity-induced DNA fragmentation. In summary, taurine regulates islet function and morphology to improve the adaptive response to diet-induced obesity, but these effects are dependent on adequate dietary protein levels.

Reduced glucose-induced insulin secretion in low-protein-fed rats is associated with altered pancreatic islets redox status.

In the present study, we investigated the relationship between early life protein malnutrition-induced redox imbalance, and reduced glucose-stimulated insulin secretion. After weaning, male Wistar rats were submitted to a normal-protein-diet (17%-protein, NP) or to a low-protein-diet (6%-protein, LP) for 60 days. Pancreatic islets were isolated and hydrogen peroxide (H2 O2 ), oxidized (GSSG) and reduced (GSH) glutathione content, CuZn-superoxide dismutase (SOD1), glutathione peroxidase (GPx1) and catalase (CAT) gene expression, as well as enzymatic antioxidant activities were quantified. Islets that were pre-incubated with H2 O2 and/or N-acetylcysteine, were subsequently incubated with glucose for insulin secretion measurement. Protein malnutrition increased CAT mRNA content by 100%. LP group SOD1 and CAT activities were 50% increased and reduced, respectively. H2 O2 production was more than 50% increased whereas GSH/GSSG ratio was near 60% lower in LP group. Insulin secretion was, in most conditions, approximately 50% lower in LP rat islets. When islets were pre-incubated with H2 O2 (100 µM), and incubated with glucose (33 mM), LP rats showed significant decrease of insulin secretion. This effect was attenuated when LP islets were exposed to N-acetylcysteine.

Taurine supplementation preserves hypothalamic leptin action in normal and protein-restricted mice fed on a high-fat diet.

Malnutrition programs the neuroendocrine axis by disruption of food-intake control, leading to obesity. Taurine (Tau) is neuroprotective and improves anorexigenic actions in the hypothalamus. We evaluated the hypothalamic gene-expression profile and food-intake control in protein-restricted mice submitted to a high-fat diet (HFD) and Tau supplementation. Mice were fed on a control (14 % protein-C) or a protein-restricted diet (6 % protein-R) for 6 weeks. Thereafter, mice received, or not, HFD for 8 weeks (CH and RH) with or without 5 % Tau supplementation (CHT and RHT). Protein restriction led to higher food intake, but calories were matched to controls. Excessive calorie intake occurred in HFD mice and this was prevented by Tau supplementation only in the CH group. Additionally, RH and CH mice developed hypothalamic leptin resistance, which was prevented by Tau. Global alterations in the expressions of genes involved in hypothalamic metabolism, cellular defense, apoptosis and endoplasmic reticulum stress pathways were induced by dietary manipulations and Tau treatment. The orexigenic peptides NPY and AgRP were increased by protein restriction and lowered by the HFD. The anorexigenic peptide Pomc was increased by HFD, and this was prevented by Tau only in CH mice. Thus, food intake was disrupted by dietary protein restriction and obesity. HFD-induced alterations were not enhanced by previous protein deficiency, but the some beneficial effects of Tau supplementation upon food intake were blunted by protein restriction. Tau effects upon feeding behavior control are complex and involve interactions with a vast gene network, preventing hypothalamic leptin resistance.

Taurine supplementation improves liver glucose control in normal protein and malnourished mice fed a high-fat diet.

SCOPE: Poor nutrition during the perinatal period is associated with an increased risk for metabolic syndrome in adulthood. Taurine (TAU) regulates ß-cell function and glucose homeo-stasis. Here, we assessed the effects of TAU supplementation upon adiposity and glucose control in malnourished mice fed a high-fat diet (HFD). METHODS AND RESULTS: Weaned male C57BL/6J mice were fed a control (14% protein - C) or a protein-restricted (6% protein - R) diet for 6 weeks. Afterwards, mice received or not an HFD for 8 weeks (CH and RH). Half of the HFDmice were supplemented with 5% TAU after weaning (CHT and RHT). Protein restriction led to typical malnutrition features. HFD increased body weight, adiposity, and led to hyperleptinemia, hyperphagia, glucose intolerance, and higher liver glucose output in RH and CH groups. Fasted R mice showed higher plasma adiponectin levels and increased phosphorylation of the AMP-activated protein kinase (p-AMPK) in the liver. These parameters were reduced in RH mice and increased p-AMPK persisted in RHT. TAU prevented obesity and improved glucose tolerance only in CHT, but liver glucose control was ameliorated in both supplemented groups. Better CHT liver glucose control was linked to increased Akt (thymoma viral proto-oncogene/protein kinase B) phosphorylation. CONCLUSION: Malnourished mice fed an HFD developed obesity, glucose intolerance, and increased liver glucose output. TAU preserved only normal liver glucose control in RHT mice, an effect associated with increased liver p-AMPK content.