<big dropzone="94Emd"><noframes id="mGh5mDn"> Skip to main page content (VSports手机版)
U.S. flag

An official website of the United States government

Dot gov

The . gov means it’s official VSports app下载. Federal government websites often end in . gov or . mil. Before sharing sensitive information, make sure you’re on a federal government site. .

Https

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely V体育官网. .

. 2013 May;48(5):435-48.
doi: 10.1007/s11745-013-3777-3. Epub 2013 Mar 29.

"VSports最新版本" Liver fatty acid binding protein gene-ablation exacerbates weight gain in high-fat fed female mice

Avery L McIntosh  1 , Barbara P Atshaves, Danilo Landrock, Kerstin K Landrock, Gregory G Martin, Stephen M Storey, Ann B Kier, Friedhelm Schroeder
Affiliations

"V体育平台登录" Liver fatty acid binding protein gene-ablation exacerbates weight gain in high-fat fed female mice

Avery L McIntosh et al. Lipids. 2013 May.

Abstract

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. VSports手机版.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest—The authors have no conflict of interest to report.

Figures

Figure 1
Figure 1. Effect of L-FABP gene-ablation and high-fat diet on body weight, percent weight gain, and liver weight in ad libitum-fed mice
Graphs of final body weight (A) and % weight gain (B) for L-FABP (+/+) (solid bars) and L-FABP (−/−) (open bars) mice on either control or high-fat diets were results from ad libitum-feeding control (black bars) or high-fat (open bars) diets. At the end of the 12 wk dietary study, livers were removed as described in the Methods. Values represent the mean ± SEM, n=5–8. Statistical analysis performed by one-way ANOVA with Bonferroni post-tests. The significance was as follows: * p≤0.05 as compared to L-FABP (+/+) control diet; # as compared to L-FABP (−/−) control diet; and $ as compared to L-FABP (+/+) high-fat diet.
Figure 2
Figure 2. Effect of L-FABP gene-ablation and high-fat diet on accumulated weight gain in ad libitum-fed mice
Mice were fed control and high-fat diets ad libitum mice as described in the Methods. The cumulative body weight wise plotted in bi-weekly intervals for L-FABP (+/+) (solid circles) and L-FABP (−/−) (open circles) mice on control (A) and high-fat (B) diets. Similarly, the weight gain/energy intake was plotted in bi-weekly intervals for L-FABP (+/+) (solid circles) and L-FABP (−/−) (open circles) mice on control (C) and high-fat (D) diets. Statistical analysis was performed by Student’s t-test with significance p ≤0.05 represented by *.
Figure 3
Figure 3. Effect of L-FABP gene-ablation and high-fat diet on distribution of lean tissue mass (LTM) and fat tissue mass (LFM) in ad libitum-fed mice
Dual emission X-ray absorptiometry (DEXA) was performed at the beginning and end of the 12 wk ad libitum-fed study. DEXA analysis results were reported as mass increases in LTM and FTM for L-FABP (+/+) and L-FABP (−/−) mice as for the (A) control and (B) high-fat diets. The mass increase per energy intake (mg/kcal) was reported as well for (C) control and (D) high-fat diets. Values represent the Mean ± SEM, n=5–7. Statistical analysis performed by one-way ANOVA with Bonferroni post-tests. The significance was as follows: * p ≤ 0.05 as compared to L-FABP (+/+) LTM; # as compared to L-FABP(−/−) LTM; and $ as compared to L-FABP (+/+) FTM.
Figure 4
Figure 4. Effects ad libitum feeding as well as L-FABP gene-ablation on key fatty acid transporters/enzymes
After termination of the 12 wk dietary study, livers from L-FABP (+/+) and L-FABP (−/−) mice on each of the different diets were harvested and expression of the several proteins involved fatty acid transport. Western blotting as described in Methods determined the levels of: (A) FATP-2, (B) FATP-4, (C) FATP-5, and (D) GOT. Representative western blots were included of each respective protein (lower lane) and normalization protein (upper lane). Values represent the mean ± SEM, n=5–8. Statistical analysis performed by one-way ANOVA with Bonferroni post-tests. The significance was as follows: * p ≤ 0.05 as compared to L-FABP (+/+) control diet; # as compared to L-FABP (−/−) control diet; and $ as compared to L-FABP (+/+) high-fat diet.
Figure 5
Figure 5. Effects of ad libitum feeding and L-FABP gene ablation on the expression levels of important fatty acid/fatty acyl CoA binding proteins
The expression levels of three LCFA/LCFA-CoA binding proteins (A) L-FABP, (B) ACBP, and (C) SCP-2 were examined by western blotting in the liver homogenates from L-FABP (+/+) and L-FABP (−/−) mice on ad libitum-fed control and high-fat diets as described in Methods. Representative western blots were included of each respective protein (lower lane) and normalization protein (upper lane). Values represent the mean ± SEM, n=5–8. Statistical analysis performed by one-way ANOVA with Bonferroni post-tests. The significance was as follows: * p ≤ 0.05 as compared to L-FABP (+/+) control diet; # as compared to L-FABP (−/−) control diet; and $ as compared to L-FABP (+/+) high-fat diet.
Figure 6
Figure 6. Effects of ad libitum feeding and L-FABP gene ablation on the expression levels of important enzymes in mitochondrial oxidation as well as on serum levels of β-hydroxybutyrate
After the end of the 12 wk dietary study, livers from L-FABP (+/+) and L-FABP (−/−) mice fed control or high-fat diets ad libitum were harvested and expression of the key mitochondrial LCFA β-oxidation enzymes was measured by western blotting as described in Methods. The effect of L-FABP gene-ablation on (A) carnitine palmitoyl transferase-1 (CPT1), (B) carnitine palmitoyl transferase-2 (CPT2), and (C) HMG-CoA synthase was examined. At the end of the dietary study, serum was also collected and levels of β-hydroxybutyrate were measured for L-FABP(+/+) and L-FABP(−/−) mice ad libitum-fed control and high-fat diets (D) as described in Methods. Representative western blots were included of each respective protein (lower lane) and normalization protein (upper lane). Values represent the mean ± SEM, n=5–8. Statistical analysis performed by one-way ANOVA with Bonferroni post-tests. The significance was as follows: * p ≤ 0.05 as compared to L-FABP (+/+) control diet; # as compared to L-FABP (−/−) control diet; and $ as compared to L-FABP (+/+) high-fat diet.
Figure 7
Figure 7. Effects of ad libitum feeding and L-FABP gene-ablation on key enzymes involved in hepatic peroxisomal oxidation of fatty acids
After termination of the 12 wk dietary study, livers from L-FABP (+/+) and L-FABP (−/−) mice ad libitum-fed control or high-fat diets were harvested and expression of the key peroxisomal fatty acid oxidation enzymes was measured by western blotting as described in Methods. The effect of L-FABP gene-ablation on (AD) ACOX1, (B) SCP-x, and (C) p-thiolase was examined. Representative western blots were included of each respective protein (lower lane) and normalization protein (upper lane). Values represent the mean ± SEM, n=5–8 in relative units of integrated density. Statistical analysis performed by one-way ANOVA with Bonferroni post-tests. The significance was as follows: * p ≤0.05 as compared to L-FABP (+/+) control diet; # as compared to L-FABP (−/−) control diet; and $ as compared to L-FABP (+/+) high-fat diet.
Figure 8
Figure 8. Effects of ad libitum feeding and L-FABP gene-ablation on the nuclear receptor, PPARα
The expression level of PPARα was determined by western blotting using livers removed from L-FABP (+/+) and L-FABP (−/−) mice at termination of the ad libitum-fed control or high-fat dietary study. Representative western blots were included of each respective protein (lower lane) and normalization protein (upper lane). Values represent the mean ± SEM, n=5–8. Statistical analysis performed by one-way ANOVA with Bonferroni post-tests. The significance was as follows: * p ≤ 0.05 as compared to L-FABP (+/+) control diet; # as compared to L-FABP (−/−) control diet; and $ as compared to L-FABP (+/+) high-fat diet.
See this image and copyright information in PMC

References

    1. Atshaves BP, Martin GG, Hostetler HA, McIntosh AL, Kier AB, Schroeder F. Liver fatty acid binding protein (L-FABP) and Dietary Obesity. Journal of Nutritional Biochemisty. 2010;21:1015–1032. - VSports手机版 - PMC - PubMed
    1. Schroeder F, Petrescu AD, Huang H, Atshaves BP, McIntosh AL, Martin GG, Hostetler HA, Vespa A, Landrock K, Landrock D, Payne HR, Kier AB. Role of fatty acid binding proteins and long chain fatty acids in modulating nuclear receptors and gene transcription. Lipids. 2008;43:1–17. - PubMed
    1. Jolly CA, Hubbell T, Behnke WD, Schroeder F. Fatty acid binding protein: stimulation of microsomal phosphatidic acid formation. Arch Biochem Biophys. 1997;341:112–121. - PubMed
    1. Jolly CA, Wilton DA, Schroeder F. Microsomal fatty acyl CoA transacylation and hydrolysis: fatty acyl CoA species dependent modulation by liver fatty acyl CoA binding proteins. Biochim Biophys Acta. 2000;1483:185–197. - PubMed
    1. Schroeder F, Jolly CA, Cho TH, Frolov AA. Fatty acid binding protein isoforms: structure and function. Chem Phys Lipids. 1998;92:1–25. - PubMed

Publication types

MeSH terms

"VSports app下载" LinkOut - more resources