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Melanocortin 1 Receptors in the Hypothalamus of Mice within the Norm and in Diet-Induced Obesity

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Abstract

The hypothalamic melanocortin system plays a key role in the regulation of eating behavior and peripheral metabolism, and its activity changes significantly in metabolic disorders. However, the possible role of the melanocortin 1 receptor (MC1R) in these processes remains unclear, while the data on the expression and localization of the MC1R in the hypothalamus of vertebrates are quite fragmentary. The aim of this work was to study the expression and distribution of MC1Rs in the hypothalamus of control mice and those with diet-induced obesity (DIO) as compared to the expression of other components of the melanocortin system and the hypothalamic localization of the microglial inflammatory (microgliosis) marker protein Iba1. DIO was induced in female C57Bl/6J mice by a 16-week diet enriched in light carbohydrates and saturated fats, which also led to impaired glucose tolerance, hyperleptinemia and hyperinsulinemia. Double fluorescence immunolabeling localized MC1Rs to pro-opiomelanocortin (POMC)-immunopositive neurons of the hypothalamic arcuate nucleus (ARC). In DIO, the amount of MC1Rs and POMC in hypothalamic neurons increased significantly. In addition, mRNA levels of MC1R, MC3R and POMC increased in the hypothalamus of DIO mice, indicative of an increase in the expression of the main melanocortin system’s components in DIO. In the hypothalamic ARC of DIO mice, the Iba1 level, as estimated by the intensity of immunohistochemical labeling, was also elevated, suggesting a relationship between MC1R signaling cascades and the activity of inflammatory processes in the hypothalamus under DIO conditions. Thus, we have established the expression of MC1Rs and their localization on POMC-immunopositive neurons of the hypothalamic ARC, as well as their increase in DIO and a possible relationship with the hypothalamic expression of POMC and Iba1. These findings may indicate the role of the MC1R as a potential regulator of peripheral metabolism and neuroinflammation under normal conditions and in metabolic disorders.

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Funding

This work was state budget funded (theme reg. no. ААА-А18-118012290427-7).

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Authors and Affiliations

  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia

    E. V. Mikhailova, K. V. Derkach, A. O. Shpakov & I. V. Romanova

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  1. E. V. Mikhailova
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  2. K. V. Derkach
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  3. A. O. Shpakov
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  4. I. V. Romanova
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Contributions

Conceptualization and experimental design (I.V.R., A.O.Sh.), data collection (E.V.M., K.V.D., I.V.R.), data processing (E.V.M., K.V.D., I.V.R.), writing and editing the manuscript (A.O.Sh., I.V.R.).

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Correspondence to I. V. Romanova.

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Translated by A. Polyanovsky

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 8, pp. 1015–1027https://doi.org/10.31857/S0869813922080052.

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Mikhailova, E.V., Derkach, K.V., Shpakov, A.O. et al. Melanocortin 1 Receptors in the Hypothalamus of Mice within the Norm and in Diet-Induced Obesity. J Evol Biochem Phys 58, 1240–1250 (2022). https://doi.org/10.1134/S0022093022040263

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