Atshaves Barbara P, McIntosh Avery L, Storey Stephen M, Landrock Kerstin K, Kier Ann B, Schroeder Friedhelm
Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX, 77843-4466, USA.
Lipids. 2010 Feb;45(2):97-110. doi: 10.1007/s11745-009-3379-2. Epub 2009 Dec 25.
Since liver fatty acid binding protein (L-FABP) facilitates uptake/oxidation of long-chain fatty acids in cultured transfected cells and primary hepatocytes, loss of L-FABP was expected to exacerbate weight gain and/or obesity in response to high dietary fat. Male and female wild-type (WT) and L-FABP gene-ablated mice, pair-fed a defined isocaloric control or high fat diet for 12 weeks, consumed equal amounts of food by weight and kcal. Male WT mice gained weight faster than their female WT counterparts regardless of diet. L-FABP gene ablation enhanced weight gain more in female than male mice-an effect exacerbated by high fat diet. Dual emission X-ray absorptiometry revealed high-fat fed male and female WT mice gained mostly fat tissue mass (FTM). L-FABP gene ablation increased FTM in female, but not male, mice-an effect also exacerbated by high fat diet. Concomitantly, L-FABP gene ablation decreased serum beta-hydroxybutyrate in male and female mice fed the control diet and, even more so, on the high-fat diet. Thus, L-FABP gene ablation decreased fat oxidation and sensitized all mice to weight gain as whole body FTM and LTM-with the most gain observed in FTM of control vs high-fat fed female L-FABP null mice. Taken together, these results indicate loss of L-FABP exacerbates weight gain and/or obesity in response to high dietary fat.
由于肝脏脂肪酸结合蛋白（L-FABP）可促进培养的转染细胞和原代肝细胞对长链脂肪酸的摄取/氧化，因此预计L-FABP的缺失会加剧因高膳食脂肪导致的体重增加和/或肥胖。将雄性和雌性野生型（WT）及L-FABP基因敲除小鼠按等热量配对喂养，分别给予对照饮食或高脂饮食12周，它们摄入的食物重量和千卡量相等。无论饮食如何，雄性WT小鼠比雌性WT小鼠体重增加得更快。L-FABP基因敲除对雌性小鼠体重增加的促进作用比对雄性小鼠更强，高脂饮食会加剧这种影响。双能X线吸收法显示，高脂喂养的雄性和雌性WT小鼠主要增加的是脂肪组织质量（FTM）。L-FABP基因敲除使雌性小鼠而非雄性小鼠的FTM增加，高脂饮食也会加剧这种影响。同时，L-FABP基因敲除使喂食对照饮食的雄性和雌性小鼠的血清β-羟基丁酸水平降低，在高脂饮食时降低得更明显。因此，L-FABP基因敲除降低了脂肪氧化，并使所有小鼠对体重增加敏感，表现为全身FTM和瘦组织质量（LTM）增加，其中对照饮食与高脂喂养的雌性L-FABP基因敲除小鼠的FTM增加最为明显。综上所述，这些结果表明L-FABP的缺失会加剧因高膳食脂肪导致的体重增加和/或肥胖。
