title: Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats.
abstract: Hypothalamic fatty acid (FA) sensing neurons alter their activity utilizing the FA translocator/receptor, FAT/CD36. Depletion of ventromedial hypothalamus (VMH) CD36 with adeno-associated viral vector expressing CD36 shRNA (AAV CD36 shRNA) leads to redistribution of adipose stores and insulin resistance in outbred rats. This study assessed the requirement of VMH CD36-mediated FA sensing for the regulation of energy and glucose homeostasis in postnatal day 5 (P5) and P21 selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats using VMH AAV CD36 shRNA injections. P5 CD36 depletion altered VMH neuronal FA sensing predominantly in DIO rats. After 10 wk on a 45% fat diet, DIO rats injected with VMH AAV CD36 shRNA at P21 ate more and gained more weight than DIO AAV controls, while DR AAV CD36 shRNA-injected rats gained less weight than DR AAV controls. VMH CD36 depletion increased inguinal fat pad weights and leptin levels in DIO and DR rats. Although DR AAV CD36 shRNA-injected rats became as obese as DIO AAV controls, only DIO control and CD36 depleted rats became insulin-resistant on a 45% fat diet. VMH CD36 depletion stunted linear growth in DIO and DR rats. DIO rats injected with AAV CD36 shRNA at P5 had increased fat mass, mostly due to a 45% increase in subcutaneous fat. They were also insulin-resistant with an associated 71% increase of liver triglycerides. These results demonstrate that VMH CD36-mediated FA sensing is a critical factor in the regulation of energy and glucose homeostasis and fat deposition in DIO and DR rats.
authors.affiliation: Department of Neurology and Neurosciences, Rutgers New Jersey Medical School, Newark, New Jersey; and christelle.lefoll@gmail.com.
authors.forename: Christelle
authors.initials: C
authors.lastname: Le Foll
authors.affiliation: Neurology Service, Veterans Affairs Medical Center, East Orange, New Jersey.
authors.forename: Ambrose A
authors.initials: AA
authors.lastname: Dunn-Meynell
authors.affiliation: Department of Neurology and Neurosciences, Rutgers New Jersey Medical School, Newark, New Jersey; and Neurology Service, Veterans Affairs Medical Center, East Orange, New Jersey.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Levin
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D018955:CD36 Antigens / Q000378:metabolism*; D004195:Disease Models, Animal; D002149:Energy Intake / Q000502:physiology*; D005227:Fatty Acids / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D020738:Leptin; D008297:Male; D009765:Obesity / Q000378:metabolism*; D051381:Rats
chemical_list: D001786:Blood Glucose; D018955:CD36 Antigens; D005227:Fatty Acids; D007328:Insulin; D020738:Leptin
keywords: CD36; fatty acid; hypothalamus; neuronal sensing; obesity