Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sterol regulatory element-binding proteins (SREBPs) are a family of membrane-bound transcription factors that regulate cholesterol and fatty acid homeostasis. In mammals, three SREBP isoforms designated SREBP-1a, SREBP-1c, and SREBP-2 have been identified. SREBP-1a and SREBP-1c are derived from the same gene by virtue of alternatively spliced first exons. SREBP-1a has a longer transcriptional activation domain and is a more potent transcriptional activator than SREBP-1c in cultured cells and liver. Here, we describe the physiologic consequences of overexpressing the nuclear form of SREBP-1a (nSREBP-1a) in adipocytes of mice using the adipocyte-specific aP2 promoter (aP2-nSREBP-1a). The transgenic aP2-nSREBP-1a mice developed markedly enlarged white and brown adipocytes that were fully differentiated. Adipocytes isolated from aP2-nSREBP-1a mice had significantly increased rates of fatty acid synthesis and enhanced fatty acid secretion. The increased production and release of fatty acids from adipocytes led, in turn, to a fatty liver. Overexpression of the alternative SREBP-1 isoform, nSREBP-1c, in adipose tissue inhibits adipocyte differentiation; as a result, the transgenic nSREBP-1c mice develop a syndrome resembling human lipodystrophy, which includes a loss of peripheral white adipose tissue, diabetes, and fatty livers (Shimomura, I., Hammer, R. E., Richardson, J. A., Ikemoto, S., Bashmakov, Y., Goldstein, J. L., and Brown, M. S. (1998) Genes Dev. 12, 3182-3194). In striking contrast, nSREBP-1a overexpression in fat resulted in the hypertrophy of fully differentiated adipocytes, no diabetes, and mild hepatic steatosis. These results suggest that nSREBP-1a and nSREBP-1c have distinct roles in adipocyte fat metabolism in vivo.
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PMID:Overexpression of sterol regulatory element-binding protein-1a in mouse adipose tissue produces adipocyte hypertrophy, increased fatty acid secretion, and fatty liver. 1285 91

Over the past 20 years obesity has become a worldwide concern of frightening proportion. The World Health Organization estimates that there are over 400 million obese and over 1.6 billion overweight adults, a figure which is projected to almost double by 2015. This is not a disease restricted to adults - at least 20 million children under the age of 5 years were overweight in 2005 (WHO 2006). Overweight and obesity lead to serious health consequences including coronary artery disease, stroke, type-2 diabetes, heart failure, dyslipidemia, hypertension, reproductive and gastrointestinal cancers, gallstones, fatty liver disease, osteoarthritis and sleep apnea (Padwal et al 2003). Modest weight loss in the obese of between 5% and 10% of bodyweight is associated with improvements in cardiovascular risk profiles and reduced incidence of type 2 diabetes (Goldstein 1992; Avenell et al 2004; Padwal and Majumdar 2007). Orlistat, a gastric and pancreatic lipase inhibitor that reduces dietary fat absorption by approximately 30%, has been approved for use for around ten years (Zhi et al 1994; Hauptman 2000). There is now a growing body of evidence to suggest that Orlistat assists weight loss and that it may also have additional benefits. The aim of this review is to provide a brief update on the current literature studying the efficacy, safety and significance of the use of Orlistat in clinical practice.
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PMID:Obesity management: update on orlistat. 1820 Aug 2