The sterol regulatory element-binding protein (SREBP) transcription factor family is a critical regulator of lipid and sterol homeostasis in eukaryotes. In mammals, SREBPs are highly active in the fed state to promote the expression of lipogenic and cholesterogenic genes and facilitate fat storage. During fasting, SREBP-dependent lipid/cholesterol synthesis is rapidly diminished in the mouse liver; however, the mechanism has remained incompletely understood. Moreover, the evolutionary conservation of fasting regulation of SREBP-dependent programs of gene expression and control of lipid homeostasis has been unclear. We demonstrate here a conserved role for orthologs of the NAD + -dependent deacetylase SIRT1 in metazoans in down-regulation of SREBP orthologs during fasting, resulting in inhibition of lipid synthesis and fat storage. Our data reveal that SIRT1 can directly deacetylate SREBP, and modulation of SIRT1 activity results in changes in SREBP ubiquitination, protein stability, and target gene expression. In addition, chemical activators of SIRT1 inhibit SREBP target gene expression in vitro and in vivo, correlating with decreased hepatic lipid and cholesterol levels and attenuated liver steatosis in dietinduced and genetically obese mice. We conclude that SIRT1 orthologs play a critical role in controlling SREBPdependent gene regulation governing lipid/cholesterol homeostasis in metazoans in response to fasting cues. These findings may have important biomedical implications for the treatment of metabolic disorders associated with aberrant lipid/cholesterol homeostasis, including metabolic syndrome and atherosclerosis. Lipids and sterols play key roles in diverse biological processes in eukaryotes, such as membrane biosynthesis, intra-and extracellular signaling, and energy storage. In humans, aberrant lipid and cholesterol homeostasis has been linked to a number of diseases prevalent in the developed world, including metabolic syndrome-a constellation of conditions and diseases that includes obesity, insulin resistance, liver steatosis, and hypertension, as well as type 2 diabetes, cardiovascular disease, and cancers (Cornier et al. 2008). An improved understanding of the molecular mechanisms governing lipid/cholesterol homeostasis might lead to novel therapeutic strategies to ameliorate such diseases.Fasting (short-term food deprivation) produces a rapid metabolic shift from lipid/cholesterol synthesis and fat storage to mobilization of fat, and recent studies have suggested that fasting may improve conditions associated with metabolic syndrome (Varady and Hellerstein 2008;Fontana et al. 2010). There is thus keen interest in determining the mechanism of fasting-dependent regulation of lipid/cholesterol metabolism to facilitate the development
Program evaluation often casts the social scientist in multiple roles that require the use of various methods and skills to deliver the product or products desired by the hiring agency. Social scientists engaged in evaluation research often find their roles being expanded beyond those articulated in their contracts. Balancing these numerous demands while maintaining professional integrity can be both challenging and rewarding in terms of professional growth and expansion of one's professional network. This article focuses on the experiences of one research team working with a law enforcement agency in a midsized city in the Southwest during the first two years of the implementation of a Weed and Seed program. Nimbleness of method, expansion of the evaluator's role, and the reality of unexpected challenges are the primary lessons to be drawn from this experience.
This article looks at the role sociologists can play as expert witnesses in the court of law. It does so by examining Agran vs. City of New York (1995), a federal civil rights case wherein original social research was undertaken specifically to establish whether the defendant did damages to the plaintiff. While the establishment of damages was secondary to the primary question of whether the plaintiff's civil rights were violated, this use of primary research in a civil case provides an interesting example of what possibilities exist for applied social researchers. Sociologists have increasingly become involved in courtroom appearances as expert witnesses. While at times their testimony is used to challenge the knowledge claims of medicine and psychology or attempts to define the limits of moral accountability of defendants (Jenkins and Kroll-Smith 1996), more often sociologists draw on their personal expertise to humanize defendants and/or help to clarify defendants 'criminal culpability (Yablonsky 2002).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.