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Importantly, amenability of C. Examining fat regulatory pathways under different environmental conditions holds the potential to reveal how physiological pathways are coordinately modulated in response to environmental perturbation.

Similarly, how developmental stage, age, experience and diet perturb and possibly rewire the fat networks can be addressed in C. elegans at a molecular level. elegans is well suited for deciphering developmental programs that underlie fat storage capacity and cell biological determinants of lipid droplet biogenesis.

Many of the adverse health effects of excess fat accumulation in humans are unlikely to occur in C. Nevertheless, the limited number of studies reported thus far already reveal remarkable similarities between molecular components of mammalian and C.

elegans fat pathways that extend to disease-associated genes. Many of the fat genes identified in C. elegans have mammalian homologs whose roles in energy balance have not yet been examined. Given that energy balance is fundamental for viability, it is likely that many of the newly identified C.

elegans fat regulatory networks are functionally conserved in mammals. I am indebted to members of the Ashrafi lab and Jennifer Watts for discussions. Edited by Andres Villu Maricq and Steven L.

Last revised November 30, Published March 9, This chapter should be cited as: Ashrafi, K. Obesity and the regulation of fat metabolism March 9, , WormBook , ed. org [ PMC free article : PMC ] [ PubMed : ]. To whom correspondence should be addressed.

Tel: , Fax: E-mail: ude. fscu ifarhsa. All WormBook content, except where otherwise noted, is licensed under a Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Show details Pasadena CA : WormBook ; Search term. Author Information and Affiliations Authors Kaveh Ashrafi , §. Affiliations 1 Department of Physiology, University of California, San Francisco, San Francisco, CA, , USA.

Obesity: an overview Obesity is a significant risk factor for major diseases including Type II diabetes, coronary heart disease, hypertension and certain forms of cancer Barsh et al.

Figure 1 Homeostatic regulation of energy balance in mammals. elegans fat 2. Fat composition Several groups have biochemically determined the composition of C. Visualization of fat droplets Whereas mammals have dedicated adipocytes, C. Figure 2 Visualization of intestinal lipid droplets in transparent bodies of C.

Genetic analysis of C. elegans fat regulation Targeted gene deletions, mutagenesis screens and a genome-scale RNA interference RNAi screen have identified approximately gene inactivations that cause fat reduction and approximately gene inactivations that cause fat accumulation without significant effects on growth and viability Ashrafi et al.

Metabolic pathways Intricate metabolic networks tightly coordinate the flow of sugars and fats through synthesis, storage, and breakdown pathways. Figure 3 Overview of fat and sugar synthesis and breakdown pathways. Breakdown pathways In general, cells break down carbohydrates, amino acids and fats to generate ATP, the universal energy resource of cells Salway, Synthesis and storage pathways Acetyl-CoA is the key substrate for synthesis of fatty acids.

Figure 5 Coordination of fat synthesis and breakdown pathways by malonyl-CoA. Table 1 Partial listing of C. Figure 4 Regulation of growth and metabolism by insulin signaling in C.

Metabolic sensors and coordinated regulation of metabolic pathways The capacity to coordinately adjust energy flux through various catabolic and anabolic pathways in response to changing nutritional status is critical for cellular and organismal survival.

elegans pathways are highlighted below: 4. sbp-1 Sterol response element binding protein SREBP is a key transcriptional regulator of fat and sterol synthesis pathways in mammals Eberle et al.

TOR, AMPK, and hexosamine pathways TOR target of rapamyacin is an evolutionarily conserved phosphatidylinositol kinase related family member that couples cell size and proliferation to nutrient levels, particularly amino acids and hormonal signals such as insulin Inoki and Guan, ; Lindsley and Rutter, Development of fat storage capacity During mammalian adipogenesis, hormonal cues initiate transcriptional programs that guide the differentiation of multipotent mesenchymal stem cells into mature adipocytes.

Neuroendocrine fat and feeding regulatory pathways In mammals, the nervous system functions as a central coordinator of both metabolic pathways and behaviors associated with food consumption. Insulin and TGF-β Signaling cascades through insulin, transforming growth factor TGF-β and cyclic nucleotide regulated pathways control whether C.

Figure 6 Systemic actions of insulin signaling in mammals. Serotonin, dopamine and glutamate pathways Classical neurotransmitters have dramatic effects on fat regulation in nemotodes and in mammals.

tub-1 and bbs-1 Mutations in rodent tubby cause progressive degeneration in retinal and cochlear sensory receptor cells, infertility and adult-onset obesity with insulin resistance Carroll et al.

Feeding behavior and fat pathways C. Perspectives Our understanding of body fat regulation as a homeostatic, organismal process has flourished in the past decade. Bibliography Allison D. Assortative mating for relative weight: genetic implications.

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nature articles article. Abstract The fate of labelled free fatty acids in isolated perfused livers shows that on entering the liver they are esterified or oxidized.

Access through your institution. Buy or subscribe. Change institution. Learn more. References Fredrickson, D. Article CAS Google Scholar Havel, R. CAS Google Scholar Morris, B. Article CAS Google Scholar Felts, J.

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