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Review

The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review

1
Biology Institute, State University of Rio de Janeiro, UERJ, Rio de Janeiro 20551-030, Brazil
2
Faculty of Applied Science, University of Campinas, UNICAMP, Campinas 13484-350, Brazil
3
Obesity and Comorbidities Research Center, University of Campinas, UNICAMP, Campinas 13083-864, Brazil
*
Authors to whom correspondence should be addressed.
Academic Editor: Paola Giussani
Int. J. Mol. Sci. 2021, 22(10), 5357; https://doi.org/10.3390/ijms22105357
Received: 24 March 2021 / Revised: 30 April 2021 / Accepted: 6 May 2021 / Published: 19 May 2021
(This article belongs to the Special Issue Sphingolipid Metabolism and Signaling in Diseases)
Obesity is a global health issue for which no major effective treatments have been well established. High-fat diet consumption is closely related to the development of obesity because it negatively modulates the hypothalamic control of food intake due to metaflammation and lipotoxicity. The use of animal models, such as rodents, in conjunction with in vitro models of hypothalamic cells, can enhance the understanding of hypothalamic functions related to the control of energy balance, thereby providing knowledge about the impact of diet on the hypothalamus, in addition to targets for the development of new drugs that can be used in humans to decrease body weight. Recently, sphingolipids were described as having a lipotoxic effect in peripheral tissues and the central nervous system. Specifically, lipid overload, mainly from long-chain saturated fatty acids, such as palmitate, leads to excessive ceramide levels that can be sensed by the hypothalamus, triggering the dysregulation of energy balance control. However, no systematic review has been undertaken regarding studies of sphingolipids, particularly ceramide and sphingosine-1-phosphate (S1P), the hypothalamus, and obesity. This review confirms that ceramides are associated with hypothalamic dysfunction in response to metaflammation, endoplasmic reticulum (ER) stress, and lipotoxicity, leading to insulin/leptin resistance. However, in contrast to ceramide, S1P appears to be a central satiety factor in the hypothalamus. Thus, our work describes current evidence related to sphingolipids and their role in hypothalamic energy balance control. Hypothetically, the manipulation of sphingolipid levels could be useful in enabling clinicians to treat obesity, particularly by decreasing ceramide levels and the inflammation/endoplasmic reticulum stress induced in response to overfeeding with saturated fatty acids. View Full-Text
Keywords: sphingolipids; lipotoxicity; central nervous system sphingolipids; lipotoxicity; central nervous system
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MDPI and ACS Style

Reginato, A.; Veras, A.C.C.; Baqueiro, M.d.N.; Panzarin, C.; Siqueira, B.P.; Milanski, M.; Lisboa, P.C.; Torsoni, A.S. The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review. Int. J. Mol. Sci. 2021, 22, 5357. https://doi.org/10.3390/ijms22105357

AMA Style

Reginato A, Veras ACC, Baqueiro MdN, Panzarin C, Siqueira BP, Milanski M, Lisboa PC, Torsoni AS. The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review. International Journal of Molecular Sciences. 2021; 22(10):5357. https://doi.org/10.3390/ijms22105357

Chicago/Turabian Style

Reginato, Andressa, Alana C.C. Veras, Mayara d.N. Baqueiro, Carolina Panzarin, Beatriz P. Siqueira, Marciane Milanski, Patrícia C. Lisboa, and Adriana S. Torsoni 2021. "The Role of Fatty Acids in Ceramide Pathways and Their Influence on Hypothalamic Regulation of Energy Balance: A Systematic Review" International Journal of Molecular Sciences 22, no. 10: 5357. https://doi.org/10.3390/ijms22105357

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