Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes.
Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance.
From the Montreal Diabetes Research Center, Centre de Recherche du Centre Hospitalier de l'Universite de Montreal and.
Bouchra
B
Taïb
Khalil
K
Bouyakdan
Cécile
C
Hryhorczuk
Demetra
D
Rodaros
Stephanie
S
Fulton
Thierry
T
Alquier
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002460:Cell Line; D004734:Energy Metabolism / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007033:Hypothalamus, Middle / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar
D005227:Fatty Acids; D055372:AMP-Activated Protein Kinases; D005947:Glucose
AMP-activated Kinase (AMPK); Astrocytes; Fatty Acid Esterification; Fatty Acid Oxidation; Glucose Metabolism; Hypothalamus; Neural Metabolism; Oleate; Palmitate