White and brown fat operation switches

The "starvation dilemma" was traced to the endomembranes

Denis Strigun, Naked Science

Experts from the University of Cambridge and the Albert Einstein College of Medicine have described the mechanism of splitting brown adipose tissue mediated by the activity of orexigenic (appetite-stimulating) neurons.

The energy balance in the mammalian body depends on the coordination of the processes of spending and receiving energy. At the molecular level, it is mediated by the decomposition of interscapular brown adipose tissue (iBAT): episodic excess of food leads to heating of its adipocytes and increased energy expenditure, limiting the growth of body weight. Hunger, on the contrary, is accompanied by delayed weight loss – this effect is often observed against the background of weight loss diets. It is known that saturation control is performed by orexigenic neurons of the hypothalamus expressing neuropeptide Y (NPY) and agoutian neuropeptide (AGRP) – so, stimulation of the latter provokes overeating. However, the neural mechanism of such regulation has not been sufficiently studied.

To find out how orexigenic neurons are connected to brown adipose tissue, the authors of a new paper published in the journal eLife conducted a series of experiments on mice. In the absence of food, animals were injected with a vector based on an adenoassociated virus (plasmid) with a fluorescent protein and an hM3dq receptor, after which clozapine-N-oxide (CNO) was injected. Under the influence of the latter, the receptor bound to AGRP neurons, which led to the depolarization of their membrane. At the same time, using a telemetric sensor implanted in the interscapular region, the scientists monitored the temperature in the brown adipose tissue. Observations showed that within an hour after such stimulation, mice consumed on average twice as much food as compared to control individuals.

The amount of food consumed after the introduction of a neutral solution and CNO (left), the temperature dynamics of brown adipocyte adipose tissue after injection of cerebrospinal fluid (aCSF) and ghrelin (from an article in eLife).

According to the hypothesis, activation of AGRP neurons reduced the temperature in adipose tissue, as well as, despite physical activity, energy consumption. A similar effect was caused by the direct injection of ghrelin into the hypothalamus, a neuropeptide that naturally stimulates AGRP. To determine the role of different molecules in the cleavage of iBAT during AGRP stimulation, the researchers treated mice with metyrosine, an inhibitor of tyrosine hydroxylase (a precursor of catecholamines): the increase in the level of adrenaline and norandrenaline accelerates the lipolysis of fats. According to the analysis, after the injection of CNO, the fat cells of the experimental mice were worse bound to norepinephrine. However, this alone did not explain the action of neurons, and the authors studied the "descending" pathways of iBAT adrenoreceptors.

Subsequent analysis He showed that stimulation of AGRP neurons is accompanied by an increase in the activity of AMP-activated protein kinase (AMPK). This enzyme regulates the energy balance of cells: when it is activated, for example during physical exertion, the cell goes into energy-saving mode. As a result, energy deficiency, stimulating the intracellular complex mTORC1 in orexigenic neurons, causes a sharp decrease in the temperature of brown adipose tissue and, as a consequence, slows down its cleavage and weight loss. Thus, the data obtained clarify the role of AGRP neurons in maintaining energy balance. In fact, these cells perform the function of a "switch" of the mechanisms of spending and storing brown fat, depending on environmental conditions.

Portal "Eternal youth" http://vechnayamolodost.ru  25.05.2017