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Brown adipose tissue (BAT) has been encouraged as a potential treatment for obesity and comorbidities due to its thermogenic activity capacity and contribution to energy expenditure. Some interventions such as cold and b-adrenergic drugs are able to activate BAT thermogenesis as well as promote differentiation of white adipocytes into brown-like cells (browning), enhancing the thermogenic activity of these cells. In this mini-review, we discuss new mechanisms related to BAT and energy expenditure. In this regard, we will also discuss recent studies that have revealed the existence of important secretory molecules from BAT “batokines” that act in autocrine, paracrine, and endocrine mechanisms, which in turn may explain some of the beneficial roles of BAT on whole body glucose and fat metabolism. Finally, we will discuss new insights related to BAT thermogenesis with an additional focus on the distinct features of BAT metabolism between rodents and humans. [ABSTRACT FROM AUTHOR]

High protein diet (HPD) is known to promote reduction of body fat but the mechanisms underlying this change are unclear. Here we show that HPD markedly reduced food intake and weight loss in both normal rats and ob/ob mice. Our data indicate that HPD signaling, through mTOR, inhibits NPY and increases POMC expression in hypothalamus. Leucine, in addition to a direct activation of mTOR, also activates mTOR through the in activation of AMPK. The intracerebroventricular administration of leucine but not other amino acids reduced food intake in a dose-dependent manner, and the magnitude of weight loss and reduction of food intake in a leucine-supplemented diet is similar to that achieved by HPD in normal rats and in ob/ob mice, suggesting that leucine is a major component of the effects of HPD. We therefore suggest that leucine supplementation presents an attractive opportunity to the treatment of obesity. [ABSTRACT FROM AUTHOR]

Recent papers reported that tyrosine kinase inhibitors used for cancer treatment may improve insulin sensitivity in type 2 diabetes. However, the molecular mechanism by which these drugs improve insulin sensitivity has not yet been established. In this study, six-week-old male Swiss mice were divided into four groups with similar body weights and assigned to receive a standard rodent chow (C) or a high fat diet (HF). After 2 months, HF-mice were treated with PD153035 (30 mg/kg) (HFPD) or vehicle (HFV) by gavage once a day for 7 day. Insulin signaling was investigated by using immunoprecipitation/immunoblotting assays. PD153035 did not change the body weight, but reduced serum insulin and plasma glucose levels compared to HF and HFV groups. Intraperitoneal GTT and ITT demonstrated improvement of insulin sensitivity in HFPD group compared to HF and HFV. Adiponectin serum levels were higher and leptin and free fatty acids serum levels were lower in HFPD group compared to HF/HFV groups. These results were associated with an increase in insulin-induced PI3-K/Akt pathway in liver, muscle and adipose tissue. In parallel we investigated the expression of pro-inflammatory cytokines and serine/kinases involved in the pathogenesis of insulin resistance. PD153035 significantly decreased tissue expression of TNFα IL-6, p-JNK and IRS-1[sup ser307] in liver, muscle and adipose tissue and TNFα and IL-6 serum levels of DIO mice. There was also a decrease in NFκB[sub 65] linked to DNA in these tissues of HFPD-mice compared to HF and HFV groups. In summary, these results demonstrate that treatment with PD153035 improve insulin sensitivity, reduces hyperglicemia and increase PI-3K/Akt pathway, in parallel to a reduction in the expression of pro-inflammatory cytokines and serine kinases involved in the pathogenesis of insulin resistance. [ABSTRACT FROM AUTHOR]