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Measurement of Basal and Forskolin-stimulated Lipolysis in Inguinal Adipose Fat Pads
Published on: July 21, 2017
Catecholamine-induced lipolysis in obesity
1Department of Medicine, Karolinska Institute at Huddinge University Hospital, Sweden.
Abstract:
Catecholamines are the only hormones with pronounced lipolytic action in man. A number of in vivo and in vitro studies suggest that there is lipolytic resistance to catecholamines in subcutaneous adipose tissue, which is the major fat depot in obese subjects. This is due to multiple alterations in catecholamine signal transduction, involving decreased expression and function of beta2-adrenoceptors, increased function of alpha2-adrenoceptors and decreased ability of cyclic monophosphate (AMP) to stimulate hormone sensitive lipase. A sedentary life-style, which usually characterizes obesity, may contribute to the catecholamine resistance. However, hereditary/genetic factors may also be involved. Recently, decreased expression and function of hormone sensitive lipase has been found in subcutaneous adipocytes of non-obese subjects with heredity for obesity. In addition, polymorphisms in the genes for beta2-adrenoceptors, beta3-adrenoceptors and hormone sensitive lipase, associate with obesity. On the other hand, catecholamine-induced lipolysis in visceral adipose tissue is increased in obesity due to increased function of beta3-adrenoceptors (major finding), decreased function of alpha2-adrenoceptors and increased ability of cyclic AMP to stimulate lipolysis. When the findings in different adipose regions are considered together, it appears that there is a redistribution of lipolysis and thereby fatty acid mobilization in obesity, favouring the visceral fat depot. This leads to an increase in the circulating fatty acid levels in the portal vein, which connects visceral fat with the liver. As a consequence, the liver function may be altered leading to hyperinsulinemia, hyperglycemia and dyslipidemia, which usually accompany the obese state.
Insights
Obesity causes resistance to catecholamine fat breakdown in subcutaneous fat but increases it in visceral fat. This redistribution favors visceral fat, potentially altering liver function and contributing to metabolic issues.
Area of Science:
- Endocrinology
- Metabolism
- Obesity Research
Background:
- Catecholamines are key hormones for lipolysis (fat breakdown) in humans.
- Obesity is associated with altered catecholamine signaling in adipose tissue.
- Subcutaneous adipose tissue, the primary fat depot in obesity, exhibits lipolytic resistance to catecholamines.
Purpose of the Study:
- To investigate the differential effects of catecholamines on lipolysis in subcutaneous versus visceral adipose tissue in obesity.
- To explore the underlying molecular mechanisms contributing to altered lipolysis in obesity.
- To understand the implications of regional fat mobilization for metabolic health.
Main Methods:
- In vivo and in vitro studies examining catecholamine signal transduction pathways.
- Analysis of adrenoceptor expression and function (beta2, alpha2, beta3).
- Assessment of cyclic AMP (cAMP) mediated stimulation of hormone-sensitive lipase (HSL).
- Investigation of genetic factors, including gene polymorphisms, associated with obesity and lipolysis.
Main Results:
- Subcutaneous adipose tissue shows reduced beta2-adrenoceptor function, increased alpha2-adrenoceptor function, and decreased cAMP-stimulated HSL activity, leading to catecholamine resistance.
- Visceral adipose tissue exhibits increased beta3-adrenoceptor function, decreased alpha2-adrenoceptor function, and enhanced cAMP-stimulated lipolysis.
- Genetic factors like polymorphisms in beta-adrenoceptor and HSL genes are linked to obesity.
Conclusions:
- Obesity causes a redistribution of lipolysis, favoring visceral fat mobilization over subcutaneous fat.
- Increased visceral lipolysis elevates portal vein fatty acid levels, potentially leading to liver dysfunction, hyperinsulinemia, hyperglycemia, and dyslipidemia.
- Understanding these regional differences in lipolysis is crucial for comprehending obesity-related metabolic complications.
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