Taurine-induced insulin signalling improvement of obese malnourished mice is associated with redox balance and protein phosphatases activity modulation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background & Aims Obese protein malnourished mice display liver insulin resistance and taurine (TAU) seems to attenuate this effect. The association between early-life malnutrition and hepatic redox balance in diet-induced insulin resistance is unknown. We investigated TAU supplementation effects upon liver redox state and insulin signalling in obese protein malnourished mice. Methods Weaned male C57BL-6 mice were fed a control (14% protein - C) or a protein-restricted diet (6% protein - R) for 6weeks. Afterwards, mice received a high-fat diet (34% fat - HFD) for 8weeks (CH - RH). Half of the HFD-mice were supplemented with TAU (5%) throughout the treatment (CHT - RHT). Body and tissues' weight, respiratory quotient (RQ), glucose tolerance and insulin sensitivity, hepatic oxidant and antioxidant markers and insulin cascade proteins were assessed. Results Protein restriction leads to typical features whereas HFD was able to induce a catch-up growth in RH. HFD-groups showed higher energy intake and adiposity, lower energy expenditure and altered RQ. Glucose tolerance and insulin sensitivity were impaired in HFD-groups and TAU attenuated these effects. H2O2 content was increased in CHT and RHT despite no differences in antioxidant enzymes and GSH concentration. AKT and PTEN phosphorylation were significantly increased in CHT but not in RHT. Conclusion Our data provide evidence for an association between TAU-induced improved glycaemic control because of PTEN inactivation and higher AKT phosphorylation. These effects seem to be related with altered hepatic redox balance in obese mice, and this effect is impaired by protein malnutrition.345771783Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)National Institute of Obesity and Diabetes (NICTOD)CEPIDFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Dominance of the hypothalamus-pituitary-adrenal axis over the renin-angiotensin-aldosterone system is a risk factor for decreased insulin secretion

Abstract How the association between the hypothalamus-pituitary-adrenal (HPA) axis and the renin-angiotensin-aldosterone system (RAAS) affects glucose metabolism were not well examined in a general population. Participants of the population-based 2015 Iwaki study were enrolled (n: 1,016; age: 54.4 ± 15.1 years). Principal component (PC) analysis identified two PCs: PC1 represented levels of the HPA axis (serum cortisol) and the RAAS (plasma aldosterone) as a whole, and PC2 represented the HPA axis relative to the RAAS (HPA axis dominance). We examined the association between these PCs and glucose metabolism using homeostasis model assessment indices of reduced insulin sensitivity (HOMA-R) and secretion (HOMA-β). Univariate linear regression analyses showed a correlation between PC2 and HOMA-β (β = −0.248, p < 0.0001), but not between PC1 and HOMA-β (β = −0.004, p = 0.9048). The correration between PC2 and HOMA-β persisted after adjustment for multiple factors (β = −0.101, p = 0.0003). No correlations were found between the PCs and HOMA-R. When subjects were tertiled based on PC2, the highest tertile was at greater risk of decreased insulin secretion (defined as the lower one third of HOMA-β (≤68.9)) than the lowest tertile after adjustment for multiple factors (odds ratio, 2.00; 95% confidence interval, 1.35–2.97). The HPA axis dominance is associated with decreased insulin secretion in a Japanese population

A genomics approach reveals insights into the importance of gene losses for mammalian adaptations

Identifying the genomic changes that underlie phenotypic adaptations is a key challenge in evolutionary biology and genomics. Loss of protein-coding genes is one type of genomic change with the potential to affect phenotypic evolution. Here, we develop a genomics approach to accurately detect gene losses and investigate their importance for adaptive evolution in mammals. We discover a number of gene losses that likely contributed to morphological, physiological, and metabolic adaptations in aquatic and flying mammals. These gene losses shed light on possible molecular and cellular mechanisms that underlie these adaptive phenotypes. In addition, we show that gene loss events that occur as a consequence of relaxed selection following adaptation provide novel insights into species' biology. Our results suggest that gene loss is an evolutionary mechanism for adaptation that may be more widespread than previously anticipated. Hence, investigating gene losses has great potential to reveal the genomic basis underlying macroevolutionary changes