Modulation of adipose tissue lipolysis and body weight by high-density lipoproteins in mice

• Published in: Nutrition & diabetes 2014-02, Vol.4 (2), p.e108-e108
• Main Authors: Wei, H, Averill, M M, McMillen, T S, Dastvan, F, Mitra, P, Subramanian, S, Tang, C, Chait, A, LeBoeuf, R C
• Format: Article
• Language: English
• Subjects: 631/443/319/2723; 631/45/287/1191; 692/699/2743/393; 692/700/565/2072; Clinical Nutrition; Diabetes; Epidemiology; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Original; original-article
• ISSN: 2044-4052; 2044-4052
• DOI: 10.1038/nutd.2014.4

Background: Obesity is associated with reduced levels of circulating high-density lipoproteins (HDLs) and its major protein, apolipoprotein (apo) A-I. As a result of the role of HDL and apoA-I in cellular lipid transport, low HDL and apoA-I may contribute directly to establishing or maintaining the obese condition. Methods: To test this, male C57BL/6 wild-type (WT), apoA-I deficient (apoA-I −/− ) and apoA-I transgenic (apoA-I tg/tg ) mice were fed obesogenic diets (ODs) and monitored for several clinical parameters. We also performed cell culture studies. Results: ApoA-I −/− mice gained significantly more body weight and body fat than WT mice over 20 weeks despite their reduced food intake. During a caloric restriction regime imposed on OD-fed mice, apoA-I deficiency significantly inhibited the loss of body fat as compared with WT mice. Reduced body fat loss with caloric restriction in apoA-I −/− mice was associated with blunted stimulated adipose tissue lipolysis as verified by decreased levels of phosphorylated hormone-sensitive lipase (p-HSL) and lipolytic enzyme mRNA. In contrast to apoA-I −/− mice, apoA-I tg/tg mice gained relatively less weight than WT mice, consistent with other reports. ApoA-I tg/tg mice showed increased adipose tissue lipolysis, verified by increased levels of p-HSL and lipolytic enzyme mRNA. In cell culture studies, HDL and apoA-I specifically increased catecholamine-induced lipolysis possibly through modulating the adipocyte plasma membrane cholesterol content. Conclusions: Thus, apoA-I and HDL contribute to modulating body fat content by controlling the extent of lipolysis. ApoA-I and HDL are key components of lipid metabolism in adipose tissue and constitute new therapeutic targets in obesity.