insulin signalling (either the insulin receptor itself or downstream components of the insulin signalling cascade) or to lipodystrophy, where the primary defect is a paucity of adipose tissue ( Savage et al . 2007 b , Semple et al . 2010 ). Owing to the
Search Results
Isabel Huang-Doran, Alison Sleigh, Justin J Rochford, Stephen O'Rahilly, and David B Savage
Maria Namwanje, Longhua Liu, Michelle Chan, Nikki Aaron, Michael J Kraakman, and Li Qiang
mass and adipocyte size. In addition, the double-knockout mice, Cbp/p300-AKO , exhibited severe lipodystrophy accompanied by hyperglycemia, hyperlipidemia and hepatic steatosis. Furthermore, we demonstrated that selective inhibition of Cbp and p300
Alex M DePaoli
) beyond obesity. The primary source of leptin production is adipose tissue. Accordingly, studies of leptin in states of ‘relative leptin deficiency’, specifically in patients with generalized or partial loss of body fat (e.g. lipodystrophy), provide
Jing Zhou, Honggui Li, Yuli Cai, Linqiang Ma, Destiny Matthews, Bangchao Lu, Bilian Zhu, Yanming Chen, Xiaoxian Qian, Xiaoqiu Xiao, Qifu Li, Shaodong Guo, Yuqing Huo, Liang Zhao, Yanan Tian, Qingsheng Li, and Chaodong Wu
of NAFLD/NASH. Similarly, the prevalence of NAFLD/NASH or even liver fibrosis is also increased among HIV-infected patients who have normal BMI or lipodystrophy ( Pérez-Matute et al. 2013 , van Welzen et al. 2019 ). In this case, HIV infection
Jeffrey Friedman
exception. This year is likely to mark the beginning of a new chapter in the biology of leptin as last February, 20 years after its discovery, leptin is now an FDA-approved human therapeutic for the treatment of severe lipodystrophy with potential for the
JM Wentworth, TP Burris, and VK Chatterjee
A recent prospective clinical study has shown that antiviral therapy with HIV protease inhibitors (PIs) is associated with a syndrome of peripheral fat wasting (lipodystrophy) and disordered glucose and lipid metabolism (Carr et al. 1999). We have studied the effects of indinavir and saquinavir, two HIV protease inhibitors, on cultured primary human preadipocytes and report that these compounds inhibit their differentiation. However, we find that these agents do not inhibit either transcriptional activation or adipocyte P2 gene induction by the PPARgamma/RXR nuclear receptor heterodimer. Together, our findings suggest that impaired adipogenesis is the basis of PI-associated lipodystrophy, but that this occurs via a PPARgamma/RXR-independent mechanism.
S Ranganathan and PA Kern
Treatment of HIV infection using protease inhibitors is frequently associated with lipodystrophy and impaired lipid and glucose metabolism. We examined the effect of saquinavir, one of the protease inhibitors, on lipid metabolism and glucose transport in cultured adipocytes. Saquinavir inhibited lipoprotein lipase (LPL) activity in 3T3-F442A and 3T3-L1 adipocytes. The inhibition of LPL was 81% at a concentration of 20 microg/ml. Another closely related drug, indinavir, had a small inhibitory effect. Saquinavir also inhibited the biosynthesis of lipids from [(14)C]-acetate. Saquinavir increased the lipolysis. Saquinavir had no significant effect on the cellular protein synthesis or protein content. Saquinavir increased the basal glucose transport threefold and decreased insulin-stimulated glucose transport by 35%. These studies suggest that some HIV protease inhibitors have direct effects on lipid and glucose metabolism. This inhibition of lipogenesis and glucose transport may explain some of the lipodystrophy, dyslipidemia and disturbed glucose metabolism with the clinical use of these drugs.
Young Hoon Son, Seok-Jin Lee, Ki-Baek Lee, Jin-Haeng Lee, Eui Man Jeong, Sun Gun Chung, Sang-Chul Park, and In-Gyu Kim
). Cav1 -deficient mice have impaired nitric oxide and calcium signaling, resulting in dilated cardiomyopathy and thickening of the alveolar septa in the lung. In humans, CAV1 mutations cause generalized lipodystrophy, insulin resistance, and
Caroline E Geisler and Benjamin J Renquist
-infected patients ( Lemoine et al. 2006 , Macias et al. 2014 , Matthews et al. 2015 , Wu et al. 2016 ). The common HIV therapeutic, highly active antiretroviral therapy (HAART), encourages lipodystrophy and can itself induce hepatic steatosis ( Vallet
K Rousseau, Z Atcha, J Denton, F R A Cagampang, A R Ennos, A J Freemont, and A S I Loudon
, Moran et al. 2004 ) have reported that in patients with generalized lipodystrophy, chronic exogenous leptin administration had no impact on bone mass density. In conclusion, our studies do not support recent investigations in rodents that have
