Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats : an effect associated with increased IL-6 levels but not with IL-10 or TNF–α

The inducible expression of the 70-kDa heat shock proteins (HSP70) is associated with homeostatically stressful situations. Stresses involving sympathetic nervous system (SNS) activation, including α1-adrenergic agonists and physical exercise, are capable of inducing HSP70 expression and release of the HSP70 inducible form, HSP72. However, whether hypoglycaemia is capable of influencing HSP70 status under a stressful situation such as insulin-induced hypoglycaemia (IIH), which also involves SNS activation, is unsettled. Hence, we decided to investigate whether the predominant signal for HSP70 expression and delivery into the blood comes from either low glucose, high insulin, or both during short-term IIH (STIIH) and long-term IIH (LTIIH). Our data indicated that low glucose level (up to 1.56 ± 0.14 mM), but not insulin, is the triggering factor responsible for a dramatic rise in HSP72 plasma concentrations (from 0.15 ± 0.01 in fed state to 0.77 ± 0.13 ng/mL during hypoglycaemic episodes). This was observed in parallel with up to 7-fold increases in interleukin-6 (IL–6) but not interleukin-10 (IL–10) or tumour necrosis factor-α (TNF–α) at STIIH. Together, the observations may suggest that HSP72 is released under hypoglycaemic conditions as a part of the homeostatic stress response, whereas at long-term, both hypoglycaemia and insulin may influence HSP72 expression in the liver, but not in kidneys. Secreted extracellular HSP72 (eHSP72) may be purely a danger signal to all the tissues of the body for the enhancement of immune and metabolic surveillance state or actively participates in glycaemic control under stressful situations

Maternal Roux-en-Y gastric bypass surgery reduces lipid deposition and increases UCP1 expression in the brown adipose tissue of male offspring

Abstract Maternal obesity induced by cafeteria diet (CAF) predisposes offspring to obesity and metabolic diseases, events that could be avoided by maternal bariatric surgery (BS). Herein we evaluated whether maternal BS is able to modulate brown adipose tissue (BAT) morphology and function in adult male rats born from obese female rats submitted to Roux-en-Y gastric bypass (RYGB). For this, adult male rat offspring were obtained from female rats that consumed standard diet (CTL), or CAF diet, and were submitted to simulated operation or RYGB. Analysis of offspring showed that, at 120 days of life, the maternal CAF diet induced adiposity and decreased the expression of mitochondrial Complex I (CI) and Complex III (CIII) in the BAT, resulting in higher accumulation of lipids than in BAT from offspring of CTL dams. Moreover, maternal RYGB increased UCP1 expression and prevented excessive deposition of lipids in the BAT of adult male offspring rats. However, maternal RYGB failed to reverse the effects of maternal diet on CI and CIII expression. Thus, maternal CAF promotes higher lipid deposition in the BAT of offspring, contributing to elevated adiposity. Maternal RYGB prevented obesity in offspring, probably by increasing the expression of UCP1

Oral free and dipeptide forms of glutamine supplementation attenuate oxidative stress and inflammation induced by endotoxemia

Objective: The aim of the present study was to determine the effects of oral supplementation with L-glutamine plus L-alanine (GLN+ALA), both in the free form and L-alanyl-L-glutamine dipeptide (DIP) in endotoxemic mice. Methods: B6.129 F2/J mice were subjected to endotoxemia (Escherichia coli lipopolysaccharide [LPS], 5 mg/kg, LPS group) and orally supplemented for 48 h with either L-glutamine (1 g/kg) plus L-alanine (0.61 g/kg) (GLN+ALA-LPS group) or 1.49 g/kg DIP (DIP-LPS group). Plasma glutamine, cytokines, and lymphocyte proliferation were measured. Liver and skeletal muscle glutamine, glutathione (GSH), oxidized GSH (GSSG), tissue lipoperoxidation (TBARS), and nuclear factor (NF)-κB–interleukin-1 receptor-associated kinase 1 (IRAK1)–Myeloid differentiation primary response gene 88 pathway also were determined.Results: Endotoxemia depleted plasma (by 71%), muscle (by 44%), and liver (by 49%) glutamine concentrations (relative to the control group), which were restored in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Supplemented groups reestablished GSH content, intracellular redox status (GSSG/GSH ratio), and TBARS concentration in muscle and liver (P < 0.05). T- and B-lymphocyte proliferation increased in supplemented groups compared with controls and LPS group (P < 0.05). Tumor necrosis factor-α, interleukin (IL)-6, IL-1 β, and IL-10 increased in LPS group but were attenuated by the supplements (P < 0.05). Endotoxemic mice exhibited higher muscle gene expression of components of the NF-κB pathway, with the phosphorylation of IκB kinase-α/β. These returned to basal levels (relative to the control group) in both GLN+ALA-LPS and DIP-LPS groups (P < 0.05). Higher mRNA of IRAK1 and MyD88 were observed in muscle of LPS group compared with the control and supplemented groups (P < 0.05). Conclusion: Oral supplementations with GLN+ALA or DIP are effective in attenuating oxidative stress and the proinflammatory responses induced by endotoxemia in mice