Targeting lipid sensing in the central nervous system: new therapy against the development of obesity and type 2 diabetes

Abstract

Introduction: The hypothalamus plays a major role in the control of energy balance, by sensing circulating lipids. Several studies conducted over the past decade suggest that disruption of lipid sensing can lead to hypothalamic lipotoxicity, thereby contributing to the development of various diseases, such as obesity and type 2 diabetes.

Areas covered: The physiological role of ‘lipid sensing' as a regulator of neuronal activity involved in the regulation of energy homeostasis will be reviewed. Next, the emerging evidence that alterations of hypothalamic systems that regulate energy balance during overnutrition can lead to the development of obesity and associated pathologies such as type 2 diabetes will be described.

Expert opinion: Several studies have highlighted the role of malonyl-CoA and PKCθ and also autophagy within the hypothalamus as signals of nutrient abundance by critical neurons regulating food intake. Besides the physiological role of hypothalamic lipid sensing, it has been shown that overnutrition can also induce hypothalamic lipotoxicity through an inflammatory process. In conclusion, lipid toxicity could be the starting point of perturbations of the central control of energy balance which will favor the appearance of obesity and type 2 diabetes. Lipid sensing in the hypothalamus could be considered as a potential target for anti-obesity/diabetic strategies.

Keywords::

• autophagy
• endoplasmic reticulum stress
• hypothalamus
• lipid sensing
• lipotoxicity
• malonyl-CoA

Acknowledgements

The authors thank the many members of the Magnan's laboratory for their contributions to the studies that were quoted in this review. We apologize to those authors whose work could not be cited owing to space limitations. The authors also thank Carl K-Y Ng for critically reading the manuscript.

Notes

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