title: Beta-adrenergic-AMPK pathway phosphorylates acetyl-CoA carboxylase in a high-epinephrine rat model, SPORTS.
abstract: We established a new animal model called SPORTS (Spontaneously-Running Tokushima-Shikoku) rats, which show high-epinephrine (Epi) levels. Recent reports show that Epi activates adenosine monophosphate (AMP)-activated protein kinase (AMPK) in adipocytes. Acetyl-CoA carboxylase (ACC) is the rate-limiting enzyme in fatty acid synthesis, and the enzymatic activity is suppressed when its Ser-79 is phosphorylated by AMPK. The aim of this study was to investigate the in vivo effect of Epi on ACC and abdominal visceral fat accumulation. We divided both 6-week male control and SPORTS rats into two groups, which were fed either normal diet or high fat and sucrose (HFS) diet for 16 weeks. At the end of diet treatment, retroperitoneal fat was collected for western blotting and histological analysis. Food intake was not different among the groups, but SPORTS rats showed significantly lower weight gain than control rats in both diet groups. After 10 weeks of diet treatment, glucose tolerance tests (GTTs) revealed that SPORTS rats had increased insulin sensitivity. Furthermore, SPORTS rats had lower quantities of both abdominal fat and plasma triglyceride (TG). In abdominal fat, elevated ACC Ser-79 phosphorylation was observed in SPORTS rats and suppressed by an antagonist of beta-adrenergic receptor (AR), propranolol, or an inhibitor of AMPK, Compound C. From these results, high level of Epi induced ACC phosphorylation mediated through beta-AR and AMPK signaling pathways in abdominal visceral fat of SPORTS rats, which may contribute to reduce abdominal visceral fat accumulation and increase insulin sensitivity. Our results suggest that beta-AR-regulated ACC activity would be a target for treating lifestyle-related diseases, such as obesity.
authors.affiliation: Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hattori
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Mawatari
authors.forename: Satomi
authors.initials: S
authors.lastname: Tsuzuki
authors.forename: Emiko
authors.initials: E
authors.lastname: Yoshioka
authors.forename: Satomi
authors.initials: S
authors.lastname: Toda
authors.forename: Masaki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Sonoko
authors.initials: S
authors.lastname: Yasui
authors.forename: Hiroko
authors.initials: H
authors.lastname: Furukawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Morishima
authors.forename: Katsushige
authors.initials: K
authors.lastname: Ono
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004435:Eating; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007328:Insulin; D011720:Pyrazoles; D011743:Pyrimidines; D011943:Receptors, Adrenergic, beta; C516138:dorsomorphin; D011433:Propranolol; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D004837:Epinephrine