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Chronic Ethanol Feeding Disrupts Both Lipid and Glucose Homeostasis in Rat Adipose Tissue

Kang, Li
http://rave.ohiolink.edu/etdc/view?acc_num=case1173388191

Abstract Details

2007, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
Chronic ethanol consumption induces hepatic steatosis and represents an independent risk factor for type 2 diabetes, associated with the disruption of lipid and glucose homeostasis. Adipose tissue acts as a regulator for maintaining whole-body lipid and glucose homeostasis; therefore, it was hypothesized that lipid and glucose homeostasis in adipose tissue might be vulnerable to chronic ethanol exposure. Increases in lipolysis, and the resulting release of free fatty acids into the circulation, have been associated with the development of insulin resistance and liver injury in other model systems. Therefore, the effects of chronic ethanol feeding on regulation of triglyceride metabolism in adipose tissue were first investigated. The current study has demonstrated that chronic ethanol feeding to rats increased the turnover rate of triglycerides in epididymal adipose tissue; the rate of triglyceride synthesis was increased 1.9-fold and the rate of triglyceride degradation was increased 3.1-fold over pair-fed controls. Triglyceride degradation is stimulated by b-adrenergic receptor activation and inhibited by insulin. Since chronic ethanol increased the rate of triglyceride degradation, it was first hypothesized that the lipolytic responses of adipocytes to b-adrenergic receptors was increased by chronic ethanol. However, chronic ethanol feeding actually suppressed b-adrenergic receptor-stimulated lipolysis, both in vivo and ex vivo. This suppression of b-adrenergic receptor-stimulated lipolysis by chronic ethanol was associated with inhibited intracellular cAMP accumulation and coincident repression of cAMP-dependent PKA activation and phosphorylation of perilipin A and HSL. These data suggest that increased stimulation of lipolysis by b-adrenergic receptors did not contribute to increased triglyceride degradation after chronic ethanol feeding. In contrast to the role of b-adrenergic agonist in the activation of lipolysis, insulin is the key inhibitor of lipolysis. The effect of chronic ethanol on the anti-lipolytic action of insulin was then studied. Chronic ethanol feeding markedly impaired insulin-mediated suppression of lipolysis in adipocytes isolated from epididymal adipose tissue, as well as in conscious rats, during a hyperinsulinemic-euglycemic clamp. Taken together, these data indicate that chronic ethanol feeding increased the rate of triglyceride degradation due to a loss in the anti-lipolytic response of adipocytes to insulin. The effects of chronic ethanol consumption on glucose homeostasis in adipose tissue were also investigated utilizing the hyperinsulinemic-euglycemic clamp technique. Hyperinsulinemic-euglycemic studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and impaired the ability of insulin to inhibit hepatic glucose production. Since adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues in mediating impaired glucose utilization after chronic ethanol feeding was further determined. While glucose disposal in skeletal muscle did not differ between pair- and ethanol-fed rats, glucose disposal in adipose tissues, including epididymal, subcutaneous, and omental depots, was decreased in ethanol-fed rats compared to pair-fed rats during the hyperinsulinemic-euglycemic clamp. These data demonstrate that chronic ethanol feeding decreased whole-body glucose utilization by impairing the utilization of glucose by adipose tissue, rather than skeletal muscle. In summary, this thesis has demonstrated that chronic ethanol feeding disrupted both lipid and glucose homeostasis in adipose tissue.
Laura Nagy (Advisor)
144 p.
ETHANOL; CHRONIC ETHANOL FEEDING; lipolysis; ADIPOSE TISSUE

Recommended Citations

Citations

  • Kang, L. (2007). Chronic Ethanol Feeding Disrupts Both Lipid and Glucose Homeostasis in Rat Adipose Tissue [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1173388191

    APA Style (7th edition)

  • Kang, Li. Chronic Ethanol Feeding Disrupts Both Lipid and Glucose Homeostasis in Rat Adipose Tissue. 2007. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1173388191.

    MLA Style (8th edition)

  • Kang, Li. "Chronic Ethanol Feeding Disrupts Both Lipid and Glucose Homeostasis in Rat Adipose Tissue." Doctoral dissertation, Case Western Reserve University, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=case1173388191

    Chicago Manual of Style (17th edition)

case1173388191
886
© 2007, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.