Regulation of energy metabolism by long-chain fatty acids

Prog Lipid Res. 2014 Jan;53:124-44. doi: 10.1016/j.plipres.2013.12.001. Epub 2013 Dec 18.


In mammals, excess energy is stored primarily as triglycerides, which are mobilized when energy demands arise. This review mainly focuses on the role of long chain fatty acids (LCFAs) in regulating energy metabolism as ligands of peroxisome proliferator-activated receptors (PPARs). PPAR-alpha expressed primarily in liver is essential for metabolic adaptation to starvation by inducing genes for beta-oxidation and ketogenesis and by downregulating energy expenditure through fibroblast growth factor 21. PPAR-delta is highly expressed in skeletal muscle and induces genes for LCFA oxidation during fasting and endurance exercise. PPAR-delta also regulates glucose metabolism and mitochondrial biogenesis by inducing FOXO1 and PGC1-alpha. Genes targeted by PPAR-gamma in adipocytes suggest that PPAR-gamma senses incoming non-esterified LCFAs and induces the pathways to store LCFAs as triglycerides. Adiponectin, another important target of PPAR-gamma may act as a spacer between adipocytes to maintain their metabolic activity and insulin sensitivity. Another topic of this review is effects of skin LCFAs on energy metabolism. Specific LCFAs are required for the synthesis of skin lipids, which are essential for water barrier and thermal insulation functions of the skin. Disturbance of skin lipid metabolism often causes apparent resistance to developing obesity at the expense of normal skin function.

Keywords: 3-hydroxy-3-methylglutaryl-CoA synthase 2; 3-oxoacyl-CoA thiolase; 6-phosphofurcto-2-kinase/fructose-2,6-bisphosphatase 3; ACAA2; ADIPOR; AF1,2; AMP-activated protein kinase; AMPK; ATF4; ATGL; Adiponectin; CD36; CPT1A; CPT1B; CREB; CaMK; D6D; DBD; DGAT; DNA binding domain; EFA; ELOVL; ETFDH; Exercise; FABP; FAS; FATP; FFAR; FGF21; FOXO1; FXR; Fasting; G protein-coupled receptor; G3P; GH; GK; GLUT4; GPR; HADHA; HMGCS2; HMW adiponectin; HNF4; HSL; IGF1; IGF1 binding protein; IGF1BP; KO; Kd; LACS; LBD; LCAD; LCFA; LPL; LXR; MCDC; MEF2; PDH; PDK; PEPCK; PFK; PFKFB3; PGC1α; PKA; PPAR; PPRE; PUFA; RAR; RXR; SCD1; SOCS2; STAT5; TNFα; TR; TRB3; TZD; UCP; VDR; VLCAD; VLDL; activating transcription factor 4; activation function 1,2; adiponectin receptor; adipose triglyceride lipase; cAMP responsive element binding protein 1; calcium/calmodulin-dependent kinase; carnitine palmitoyltransferase 1A (liver type); carnitine palmitoyltransferase 1B (muscle type); delta-6 desaturase (also called FADS2); diacylglycerol acyltransferase; dissociation constant; electron-transferring flavoprotein dehydrogenase; elongation of very-long chain; essential fatty acid; farnesoid-X receptor; fatty acid binding protein; fatty acid synthase; fatty acid transfer protein; fatty acid translocase; fibroblast growth factor 21; forkhead box O1; free fatty acid receptor; gene knockout; glucokinase; glucose transporter 4; glycerol-3-phosphate; growth hormone; hepatocyte nuclear factor 4; high molecular weight adiponectin (up to 18mer); hormone sensitive lipase; insulin-like growth factor 1; ligand binding domain; lipoprotein lipase; liver-X receptor; long chain acyl-CoA dehydrogenase; long chain acyl-CoA synthase; long chain fatty acid (C=14–20); malonyl-CoA decarboxylase; myocyte enhancer factor 2; peroxisome proliferator response element; peroxisome proliferator-activated receptor; peroxisome proliferator-activated receptor gamma coactivator 1α; phosphoenolpyruvate carboxykinase; phosphofructokinase; polyunsaturated fatty acid; protein kinase A; pyruvate dehydrogenase; pyruvate dehydrogenase kinase; retinoic acid receptor; retinoid-X receptor; signal transducer and activator of transcription 5; stearoyl-CoA desaturase 1; suppressor of cytokine signaling 2; thiazolidinedione; thyroid hormone receptor; tribbles homolog 3; trifunctional protein α subunit; tumor necrosis factor alpha; uncoupling protein; very long chain acyl-CoA dehydrogenase; very low density lipoprotein; vitamin D receptor.

Publication types

  • Review

MeSH terms

  • Animals
  • Energy Metabolism*
  • Fasting / metabolism
  • Fasting / physiology
  • Fatty Acids / chemistry*
  • Fatty Acids / metabolism*
  • Humans
  • Ligands
  • Organ Specificity
  • Receptors, Cytoplasmic and Nuclear / metabolism


  • Fatty Acids
  • Ligands
  • Receptors, Cytoplasmic and Nuclear