Beta-adrenergic-AMPK pathway phosphorylates acetyl-CoA carboxylase in a high-epinephrine rat model, SPORTS.
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.
Hattori
Atsushi
A
Department of Nutrition and Metabolism, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima, Japan.
Mawatari
Kazuaki
K
Tsuzuki
Satomi
S
Yoshioka
Emiko
E
Toda
Satomi
S
Yoshida
Masaki
M
Yasui
Sonoko
S
Furukawa
Hiroko
H
Morishima
Masaki
M
Ono
Katsushige
K
Ohnishi
Takamasa
T
Nakano
Masayuki
M
Harada
Nagakatsu
N
Takahashi
Akira
A
Nakaya
Yutaka
Y
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
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