Lipoexpediency: de novo lipogenesis as a metabolic signal transmitter - PubMed (original) (raw)

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Lipoexpediency: de novo lipogenesis as a metabolic signal transmitter

Irfan J Lodhi et al. Trends Endocrinol Metab. 2011 Jan.

Abstract

De novo lipogenesis, the production of fats from simple precursors, is often dismissed as irrelevant to the pathobiology of obesity caused by positive energy balance due to typical high fat diets. However, emerging data implicate de novo lipogenesis in the generation of metabolic signals that alter disease risk. Exploiting this signaling pathway represents lipoexpediency. Lipoexpediency is the concept of directing fats toward benefit even in the setting of lipid overload, and represents a strategy to complement efforts aimed at improving energy balance. Optimizing lipid signals initiated by key lipogenic enzymes such as fatty acid synthase might limit morbidity in people who are unlikely to abandon the lifestyle of the sedentary gourmand.

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Figures

Figure 1

Figure 1

Schematic of pathways involved in de novo lipogenesis. ACL-ATP citrate lyase; ACC-acetyl-CoA carboxylase; FAS-fatty acid synthase; SCD-1-stearyl-CoA desaturase; Elovl6-elongation of very long-chain fatty acids protein 6.

Figure 2

Figure 2

FAS generates an endogenous ligand for PPARα in liver. FAS, a homodimer, synthesizes palmitate, which is converted to a CoA species that is incorporated into diacylglycerol (DAG). CDP-choline is generated by the sequential actions of CK (choline kinase) and CCT (CTP:phosphocholine cytidylyltransferase), enzymes in the Kennedy pathway of phosphatidylcholine synthesis. DAG and CDP-choline are converted by the ER protein choline-ethanolamine phosphotransferase-1 (CEPT1) to 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine. This phosphatidylcholine species binds to PPARα, which forms a heterodimer with RXR to activate gene expression.

Figure 3

Figure 3

De novo lipogenesis as a potential mediator of lipoexpediency. (a) Inactivity, obesity, and overeating tip energy balance away from the benefits of proper diet and exercise, leading to lipid overload and tissue damage induced by lipotoxicity. (b) The appropriate manipulation of de novo lipogenesis pathways has the potential to generate beneficial lipid transmitters with the capacity to tip metabolic scales in favor of greater benefit from diet and exercise and leading to the integrative physiology of lipoexpediency.

Figure 4

Figure 4

Potential effector mechanisms of lipoexpediency. Tissue specific modulation of de novo lipogenesis has the potential to decrease fatty liver and insulin resistance by altering PPAR signals, affecting insulin sensitivity through lipokine production, dampening feeding behavior through the synthesis of signaling lipids (such as oleoylethanolamide [OEA] and C16:0 N-acylphosphatidylethanolamine [NAPE]), and decreasing organ pathology through several effects on protein modification.

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References

    1. Cowie CC, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005-2006. Diabetes Care. 2009;32:287–294. - PMC - PubMed
    1. Ford ES, et al. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA. 2002;287:356–359. - PubMed
    1. Stewart ST, et al. Forecasting the effects of obesity and smoking on U.S. life expectancy. N Engl J Med. 2009;361:2252–2260. - PMC - PubMed
    1. Yang W, et al. Prevalence of diabetes among men and women in China. N Engl J Med. 2010;362:1090–1101. - PubMed
    1. Fabbrini E, et al. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010;51:679–689. - PMC - PubMed

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