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CNS GNPDA2 Does Not Control Appetite, but Regulates Glucose Homeostasis
Ruth Gutierrez-Aguilar1,2, Bernadette E Grayson3, Dong-Hoon Kim4
1División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Mexico City, Mexico.
Frontiers in Nutrition
|December 16, 2021
Summary
Glucosamine-6-phosphate deaminase 2 (GNPDA2) regulates glucose homeostasis but not appetite. Inhibition of GNPDA2 in the brain leads to glucose intolerance, suggesting a key role in metabolic control.
Area of Science:
- Metabolic regulation
- Neuroendocrinology
- Obesity and Diabetes research
Background:
- The enzyme glucosamine-6-phosphate deaminase 2 (GNPDA2) is linked to obesity and type-2 diabetes.
- GNPDA2 and GFAT are involved in the hexosamine biosynthesis pathway, crucial for nutrient sensing and insulin resistance.
Purpose of the Study:
- To investigate the roles of GNPDA2 and GFAT in central nervous system (CNS) nutrient sensing circuits.
- To determine their effects on appetite regulation and glucose homeostasis.
Main Methods:
- Administered GNPDA2 or GFAT antagonists or vehicle into the third ventricle (i3vt) of Long Evans rats.
- Analyzed gene expression in hypothalamus and other tissues.
- Measured c-Fos expression in hypothalamic nuclei and assessed food intake, body weight, and glucose tolerance.
Main Results:
- GNPDA2 is highly expressed in the hypothalamus, downregulated in diet-induced obesity.
- Central inhibition of GNPDA2 did not affect appetite or body weight but caused glucose intolerance.
- GFAT inhibition reduced appetite and body weight, associated with visceral illness.
Conclusions:
- Central GNPDA2 plays a role in regulating glucose homeostasis, independent of appetite control.
- GFAT inhibition centrally impacts appetite and body weight, potentially via visceral illness.
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