Lipid Metabolism

11β-Hydroxysteroid dehydrogenase type 1 and 2 (11β-HSD1 and 2) are involved in the conversion of cortisone (Product No. C2755) to cortisol (Product No. H0135). 11β-HSD1 is expressed in adipose tissue. Overexpression of the enzyme and increased glutacorticoid levels results in lipid accumulation and an increase in visceral adipocytes1. Chronically elevated glucocorticoid levels cause Cushing’s syndrome, a disease caused by excessive cortisol production that triggers obesity, skin darkening, muscle weakness and fatigue. Thus, inhibiting 11β-HSD1 in adipose tissue could prove a viable therapy for treating both this disease and visceral obesity. Acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT1) acts as a key enzyme in the synthesis of triglycerides, the main form of excess calorie storage in fat. DGAT1 is also expressed in adipocytes and overexpression causes increased triglyceride levels. DGAT1-deficient mice exhibit increased insulin (Product No. I1507) and leptin (Product No. L4146) sensitivity and resistance to diet-induced obesity due to increased energy expenditure2.

Since dietary fat constitutes 35-45% of energy intake, another therapeutic approach for the treatment of obesity is to inhibit the absorption of fat from the gut. Digestion of dietary fat occurs through the activation of two enzymes: gastric lipases, secreted in the stomach, and pancreatic lipases, secreted in the duodenum. Orlistat (Product No. O4139), a pancreatic and gastric lipase inhibitor approved by the FDA in 1999, reduces dietary fat absorption, thereby decreasing hydrolysis of ingested triglycerides3. Fatty acids and fatty acid metabolism may influence food intake and metabolic pathways through functions in the brain. Fatty acid synthase (FAS) inhibitors reduce food intake, body weight and body fat by altering the expression of hypothalamic neuropeptides such as NPY/AgRP, MCH (Product No. M4135), α-MSH (Product No. M2567) and POMC/CART. FAS substrates inhibit the mitochondrial enzyme carnitine palmitoyl transferase I (CPT I), increasing the levels of long chain acyl CoA derivatives levels [4]. Malonyl CoA (Product No. M4263) regulates CPT its formation and is regulated by acetyl CoA carboxylase (ACC). Mice deficient in this enzyme produce less malonyl CoA, which in turn increases CPT I and reduces long chain acyl CoA derivative levels, causing an increase in the rate of lipid oxidation4.




  1. Stewart, P.M. and Tomlinson, J.W., Cortisol, 11β-hydroxysteroid dehydrogenase type 1 and central obesity. Trends Endocrinol. Metab. , 13, 94-96 (2002).
  2. Yu, Y.-H., et al., Posttranscriptional control of the expression and function of diacylglycerol acyltransferase-1 in mouse adipocytes. J. Biol. Chem, 277, 50876-50884 (2002).
  3. Finer, N., Pharmacotherapy of obesity. Best Pract. Res. Clin. Endocrinol. Metab., 16, 717-742 (2002).
  4. Flier, J.S., Obesity Wars: Molecular progress confronts an expanding epidemic. Cell, 116, 337-350 (2004).


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