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Key points: Melanin‐concentrating hormone (MCH) neuron‐ablated mice exhibit increased energy expenditure and reduced fat weight.Increased brown adipose tissue (BAT) activity and locomotor activity‐independent energy expenditure contributed to body weight reduction in MCH neuron‐ablated mice.MCH neurons send inhibitory input to the medullary raphe nucleus to modulate BAT activity. Hypothalamic melanin‐concentrating hormone (MCH) peptide robustly affects energy homeostasis. However, it is unclear whether and how MCH‐producing neurons, which contain and release a variety of neuropeptides/transmitters, regulate energy expenditure in the central nervous system and peripheral tissues. We thus examined the regulation of energy expenditure by MCH neurons, focusing on interscapular brown adipose tissue (BAT) activity. MCH neuron‐ablated mice exhibited reduced body weight, increased oxygen consumption, and increased BAT activity, which improved locomotor activity‐independent energy expenditure. Trans‐neuronal retrograde tracing with the recombinant pseudorabies virus revealed that MCH neurons innervate BAT via the sympathetic premotor region in the medullary raphe nucleus (MRN). MRN neurons were activated by MCH neuron ablation. Therefore, endogenous MCH neuron activity negatively modulates energy expenditure via BAT inhibition. MRN neurons might receive inhibitory input from MCH neurons to suppress BAT activity. [ABSTRACT FROM AUTHOR]

Macronutrient intake is associated with cardiometabolic health, ageing and longevity, but the mechanisms underlying its regulation have remained unclear. Most rodents increase carbohydrate selection under certain physiological and pathological conditions such as fasting. When presented with a choice between a basally preferable high‐fat diet (HFD) and a high‐carbohydrate diet (HCD) such as a high‐sucrose diet, fasted mice first eat the HFD and then switch to the HCD during the first few hours of refeeding and continue to eat the HCD up to 24 h in the two‐diet choice approach. Such consumption of an HCD after fasting reverses the fasting‐induced increase in the plasma concentration of ketone bodies more rapidly than does refeeding with an HFD alone. 5′‐AMP‐activated protein kinase (AMPK)‐regulated neurons in the paraventricular nucleus of the hypothalamus (PVH) that express corticotropin‐releasing hormone (CRH) are necessary and sufficient for the fasting‐induced selection of carbohydrate over an HFD in mice. These neurons appear to contribute to a fasting‐induced increase in the positive valence of carbohydrate without affecting the preference for more palatable and energy‐dense diets such as an HFD. Identification of the neural circuits in which AMPK‐regulated CRH neurons in the PVH of mice are embedded should shed new light on the physiological and molecular mechanisms responsible for macronutrient selection. [ABSTRACT FROM AUTHOR]

The article discusses a study on the structural basis for compound C inhibition of the human AMP-activated protein kinase (AMPK) α2 subunit kinase domain. AMPK is described as a serine/threonine kinase functioning as a sensor to maintain energy balance at the cellular and whole-body levels. The authors say that AMPK is a potential target for drug design against metabolic syndrome, obesity and type 2 diabetes.

The effects of L-glutamate and insulin on glycogen synthesis in astrocytes were examined. L-Glutamate and insulin both stimulated glycogen synthesis in primary cultures of rat astrocytes in a dose-dependent manner, as measured by the incorporation of 14C from [14C]glucose into glycogen. D-Aspartate also increased the incorporation of 14C into glycogen. When insulin and L-glutamate were added together, the glycogen synthesis as well as glycogen content of the cells was additively increased. Wortmannin, an inhibitor of phosphatidylinositol 3-kinase, had little effect on glycogen synthesis induced by L-glutamate, whereas it suppressed the insulin-induced glycogen synthesis. These results suggest that the insulin- and L-glutamate-induced glycogen syntheses are mediated by different intracellular mechanisms. In fact, insulin stimulated the conversion of glycogen synthase b to glycogen synthase a, which was suppressed by wortmannin. L-Glutamate and D-aspartate, however, did not increase the level of glycogen synthase a activity. By contrast, L-glutamate increased 2-deoxy-D-[3H]glucose uptake by the astrocytes, whereas insulin did not affect the uptake. These results suggest that insulin stimulates glycogen synthesis in astrocytes by activating glycogen synthase, which is dependent on a wortmannin-sensitive signaling pathway. L-Glutamate, however, enhances the glucose uptake, which contributes to the increase in glycogen synthesis in the cells. [ABSTRACT FROM AUTHOR]