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Liver Fatty Acid Binding Protein Gene‐Ablation Exacerbates Weight Gain in High‐Fat Fed Female Mice
Author(s) -
McIntosh Avery L.,
Atshaves Barbara P.,
Landrock Danilo,
Landrock Kerstin K.,
Martin Gregory G.,
Storey Stephen M.,
Kier Ann B.,
Schroeder Friedhelm
Publication year - 2013
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/s11745-013-3777-3
Subject(s) - medicine , endocrinology , weight gain , beta oxidation , peroxisome , fatty acid binding protein , fatty acid synthase , adipose tissue , biology , carnitine , fatty acid , fatty acid metabolism , fatty liver , steatosis , lipid metabolism , metabolism , biochemistry , body weight , gene , receptor , disease
Loss of liver fatty acid binding protein (L‐FABP) decreases long chain fatty acid uptake and oxidation in primary hepatocytes and in vivo. On this basis, L‐FABP gene ablation would potentiate high‐fat diet‐induced weight gain and weight gain/energy intake. While this was indeed the case when L‐FABP null (−/−) mice on the C57BL/6NCr background were pair‐fed a high‐fat diet, whether this would also be observed under high‐fat diet fed ad libitum was not known. Therefore, this possibility was examined in female L‐FABP (−/−) mice on the same background. L‐FABP (−/−) mice consumed equal amounts of defined high‐fat or isocaloric control diets fed ad libitum. However, on the ad libitum‐fed high‐fat diet the L‐FABP (−/−) mice exhibited: (1) decreased hepatic long chain fatty acid (LCFA) β‐oxidation as indicated by lower serum β‐hydroxybutyrate level; (2) decreased hepatic protein levels of key enzymes mitochondrial (rate limiting carnitine palmitoyl acyltransferase A1, CPT1A; HMG‐CoA synthase) and peroxisomal (acyl CoA oxidase 1, ACOX1) LCFA β‐oxidation; (3) increased fat tissue mass (FTM) and FTM/energy intake to the greatest extent; and (4) exacerbated body weight gain, weight gain/energy intake, liver weight, and liver weight/body weight to the greatest extent. Taken together, these findings showed that L‐FABP gene‐ablation exacerbated diet‐induced weight gain and fat tissue mass gain in mice fed high‐fat diet ad libitum—consistent with the known biochemistry and cell biology of L‐FABP.