Lipoexpediency: de novo lipogenesis as a metabolic signal transmitter - PubMed (original) (raw)
Review
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.
Figures
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
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
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
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.
Similar articles
- Brain lipogenesis and regulation of energy metabolism.
López M, Vidal-Puig A. López M, et al. Curr Opin Clin Nutr Metab Care. 2008 Jul;11(4):483-90. doi: 10.1097/MCO.0b013e328302f3d8. Curr Opin Clin Nutr Metab Care. 2008. PMID: 18542011 Review. - Fine-tuning the lipogenic/lipolytic balance to optimize the metabolic requirements of cancer cell growth: molecular mechanisms and therapeutic perspectives.
Menendez JA. Menendez JA. Biochim Biophys Acta. 2010 Mar;1801(3):381-91. doi: 10.1016/j.bbalip.2009.09.005. Epub 2009 Sep 24. Biochim Biophys Acta. 2010. PMID: 19782152 Review. - CD147 reprograms fatty acid metabolism in hepatocellular carcinoma cells through Akt/mTOR/SREBP1c and P38/PPARα pathways.
Li J, Huang Q, Long X, Zhang J, Huang X, Aa J, Yang H, Chen Z, Xing J. Li J, et al. J Hepatol. 2015 Dec;63(6):1378-89. doi: 10.1016/j.jhep.2015.07.039. Epub 2015 Aug 15. J Hepatol. 2015. PMID: 26282231 - Gene expressions of de novo hepatic lipogenesis in feline hepatic lipidosis.
Valtolina C, Robben JH, van Wolferen ME, Kruitwagen HS, Corbee RJ, Favier RP, Penning LC. Valtolina C, et al. J Feline Med Surg. 2020 Jun;22(6):500-505. doi: 10.1177/1098612X19857853. Epub 2019 Jul 19. J Feline Med Surg. 2020. PMID: 31322470 Free PMC article. - CYP4F3B expression is associated with differentiation of HepaRG human hepatocytes and unaffected by fatty acid overload.
Madec S, Cerec V, Plée-Gautier E, Antoun J, Glaise D, Salaun JP, Guguen-Guillouzo C, Corlu A. Madec S, et al. Drug Metab Dispos. 2011 Oct;39(10):1987-96. doi: 10.1124/dmd.110.036848. Epub 2011 Jul 21. Drug Metab Dispos. 2011. PMID: 21778351
Cited by
- Coffee pulp improves glucose and lipid metabolism disorder in high-fat diet-induced diabetic mice.
Zhu S, Wang C, Meng ZX. Zhu S, et al. Metabol Open. 2024 Jul 31;23:100303. doi: 10.1016/j.metop.2024.100303. eCollection 2024 Sep. Metabol Open. 2024. PMID: 39188638 Free PMC article. - Hydroxytyrosol Linoleoyl Ether Ameliorates Metabolic-Associated Fatty Liver Disease Symptoms in Obese Zucker Rats.
Tovar R, de Ceglia M, Rodríguez-Pozo M, Vargas A, Gavito A, Suárez J, Boronat A, de la Torre R, de Fonseca FR, Baixeras E, Decara J. Tovar R, et al. ACS Pharmacol Transl Sci. 2024 Apr 4;7(5):1571-1583. doi: 10.1021/acsptsci.4c00105. eCollection 2024 May 10. ACS Pharmacol Transl Sci. 2024. PMID: 38751648 - Effects of Rosa multiflora root extract on adipogenesis and lipogenesis in 3T3-L1 adipocytes and SD rat models.
Kim KK, Lee HR, Jang SM, Kim TW. Kim KK, et al. Nutr Res Pract. 2024 Apr;18(2):180-193. doi: 10.4162/nrp.2024.18.2.180. Epub 2024 Mar 21. Nutr Res Pract. 2024. PMID: 38584817 Free PMC article. - Longitudinal aortic strain, ventriculo-arterial coupling and fatty acid oxidation: novel insights into human cardiovascular aging.
Zhang H, Leng S, Gao F, Kovalik JP, Tan RS, Wee HN, Chua KV, Ching J, Zhao X, Allen J, Wu Q, Leiner T, Zhong L, Koh AS. Zhang H, et al. Geroscience. 2024 Mar 22. doi: 10.1007/s11357-024-01127-x. Online ahead of print. Geroscience. 2024. PMID: 38514519 - CDK6 inhibits de novo lipogenesis in white adipose tissues but not in the liver.
Hu AJ, Li W, Dinh C, Zhang Y, Hu JK, Daniele SG, Hou X, Yang Z, Asara JM, Hu GF, Farmer SR, Hu MG. Hu AJ, et al. Nat Commun. 2024 Feb 5;15(1):1091. doi: 10.1038/s41467-024-45294-z. Nat Commun. 2024. PMID: 38316780 Free PMC article.
References
- 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
- Yang W, et al. Prevalence of diabetes among men and women in China. N Engl J Med. 2010;362:1090–1101. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- P30 DK056341/DK/NIDDK NIH HHS/United States
- F32 DK083895/DK/NIDDK NIH HHS/United States
- DK088083/DK/NIDDK NIH HHS/United States
- R01 DK076729/DK/NIDDK NIH HHS/United States
- R01 DK088083/DK/NIDDK NIH HHS/United States
- R01 DK076729-04/DK/NIDDK NIH HHS/United States
- DK076729/DK/NIDDK NIH HHS/United States
- P30 DK056341-10/DK/NIDDK NIH HHS/United States
- R01 DK088083-02/DK/NIDDK NIH HHS/United States
LinkOut - more resources
Full Text Sources