Chronic ethanol and triglyceride turnover in white adipose tissue in rats: inhibition of the anti-lipolytic action of insulin after chronic ethanol contributes to increased triglyceride degradation.
Chronic ethanol consumption disrupts whole-body lipid metabolism. Here we tested the hypothesis that regulation of triglyceride homeostasis in adipose tissue is vulnerable to long-term ethanol exposure. After chronic ethanol feeding, total body fat content as well as the quantity of epididymal adipose tissue of male Wistar rats was decreased compared with pair-fed controls. Integrated rates of in vivo triglyceride turnover in epididymal adipose tissue were measured using (2)H(2)O as a tracer. Triglyceride turnover in adipose tissue was increased due to a 2.3-fold increase in triglyceride degradation in ethanol-fed rats compared with pair-fed controls with no effect of ethanol on triglyceride synthesis. Because increased lipolysis accompanied by the release of free fatty acids into the circulation is associated with insulin resistance and liver injury, we focused on determining the mechanisms for increased lipolysis in adipose tissue after chronic ethanol feeding. Chronic ethanol feeding suppressed beta-adrenergic receptor-stimulated lipolysis in both in vivo and ex vivo assays; thus, enhanced triglyceride degradation during ethanol feeding was not due to increased beta-adrenergic-mediated lipolysis. Instead, chronic ethanol feeding markedly impaired insulin-mediated suppression of lipolysis in conscious rats during a hyperinsulinemic-euglycemic clamp as well as in adipocytes isolated from epididymal and subcutaneous adipose tissue. These data demonstrate for the first time that chronic ethanol feeding increased the rate of triglyceride degradation in adipose tissue. Furthermore, this enhanced rate of lipolysis was due to a suppression of the anti-lipolytic effects of insulin in adipocytes after chronic ethanol feeding.
Departments of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106; Departments of Pathobiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195.
Li
L
Kang
Departments of Pathobiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195; Departments of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106.
Xiaocong
X
Chen
Departments of Pathobiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195.
Becky M
BM
Sebastian
Departments of Pathobiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195.
Brian T
BT
Pratt
Departments of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106.
Ilya R
IR
Bederman
Departments of Mathematics, Case Western Reserve University, Cleveland, Ohio 44106.
James C
JC
Alexander
Departments of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106.
Stephen F
SF
Previs
Departments of Gastroenterology, Cleveland Clinic Foundation, Cleveland, Ohio 44195; Departments of Pathobiology, Cleveland Clinic Foundation, Cleveland, Ohio 44195; Departments of Nutrition, Case Western Reserve University, Cleveland, Ohio 44106. Electronic address: laura.nagy@case.edu.
Laura E
LE
Nagy
D052438:Adipocytes, White / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism; D015309:Glucose Clamp Technique; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D007333:Insulin Resistance; D008066:Lipolysis / Q000187:drug effects*; D008099:Liver / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism* / Q000473:pathology; D014280:Triglycerides / Q000378:metabolism*
D002492:Central Nervous System Depressants; D005227:Fatty Acids; D007004:Hypoglycemic Agents; D007328:Insulin; D011943:Receptors, Adrenergic, beta; D014280:Triglycerides; D000431:Ethanol