According to a publication in Cell Metabolism, the enzyme HSL (hormone-sensitive lipase) has a previously unknown function. This opens prospects for developing fundamentally new methods for combating excess weight. A New Vector for Weight Loss Has Been Found Area of Study The function of HSL is to initiate the breakdown of fat reserves when the body requires energy, for example, during starvation or stress. Normally, HSL is present in the cytoplasm (the internal contents of the cell) and is activated by adrenaline and other hormones. In individuals suffering from obesity, a decrease in the amount of HSL is often observed. This seems a logical consequence: weakened enzyme activity accelerates fat accumulation. However, in the complete absence of HSL, patients develop the opposite condition—lipodystrophy, in which the body is extremely limited in its ability to deposit fat. This paradox indicated the presence of hidden, unexplored roles for the enzyme. Key Discovery The research group established that a portion of HSL molecules is localized not in the cytoplasm, but inside the nucleus of adipocytes (fat cells). The nucleus is the cell’s control center, where genetic material is concentrated. Upon entering the nucleus, HSL begins to regulate genes responsible for the correct deposition of energy by the fat cell and the maintenance of normal tissue structure. Without this nuclear component of HSL, the cell loses the ability to adequately assess the required volume of fat deposits. This is why people with a complete HSL deficiency have virtually no fatty tissue. Conversely, in obesity, control over this process may be lost. Thus, the study demonstrates that HSL performs not one, but two critically important tasks: it promotes lipolysis and simultaneously carries out molecular control over genome function within the nucleus. Results of Animal Model Experiments Mice lacking HSL had almost no fat reserves. Their adipocytes were unable to accumulate energy, which prevented the formation of adipose tissue. Mice with obesity showed the opposite picture: excess HSL accumulated in the nuclei of their fat cells. This concentration overshoot provoked mitochondrial dysfunction (the cell’s energy centers) and нарушения (disorders) in glucose level regulation. The data obtained emphasize that precise dosing of HSL is important for the fat cell. Both a deficiency and an excess of the enzyme lead to pathologies that alter the metabolic characteristics of the tissue in terms of energy accumulation and expenditure. Potential for Therapeutic Application The next stage of the work involves analyzing this relationship at different stages of obesity development and assessing the dynamics of nuclear HSL levels in animals with varying degrees of metabolic disorders. The scientists also intend to develop a method to modulate HSL concentration directly in the nucleus. Developers believe that the ability to precisely control HSL could become the basis for future therapeutic strategies. The focus is shifting from simply burning excess fat to restoring the homeostasis of fat cells. This approach has the potential to prevent the development of obesity-related complications.
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