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Effect of medium- and long-chain fatty acid diets on PPAR and SREBP-1 expression and glucose homeostasis in ACBP-overexpressing transgenic rats.
Acta Physiol (Oxf). 2008 Sep; 194(1):57-65.AP

Abstract

AIM

Acyl-CoAs are important intermediates and regulators of lipid metabolism. Binding proteins like acyl-CoA binding protein (ACBP) can influence their regulatory functions. ACBP has also been shown to exert direct effects on gene regulation in vitro. As the physiological relevance of ACBP in the regulation of lipid metabolism under high fat diets is unclear, we investigated the influence of such diets on the metabolic responses in ACBP-overexpressing rats.

METHODS

A transgenic rat line overexpressing the ACBP gene was used to study the effects of 4 weeks of feeding with medium- (MC) or long-chain (LC) fatty acid-containing diets. Glucose tolerance tests were performed. Expression of transcription factors was measured by quantitative RT-PCR and protein levels of AMP-activated protein kinase were determined by western blotting.

RESULTS

Transgenic animals fed the MC diet had an improved glucose tolerance and lower serum insulin levels compared with controls. Their liver PPARgamma (by 43%) and SREBP-1 (by 35%) mRNA levels were found to be decreased, while adipose tissue PPARgamma expression was increased by 31%. Tg animals fed the LC diet did not exhibit changes in glucose or insulin levels but exhibited increased mRNA levels of liver PPARs and SREBP-1 (1.5-3.5 times) and decreased protein levels of AMPKalpha (by 48%).

CONCLUSIONS

Our results demonstrate that ACBP overexpression affects metabolic responses to diets with distinct difference in their fatty acid chain lengths. The molecular regulatory mechanism behind these effects seems to be an ACBP-induced tissue-specific regulation of expression of PPARs and SREBP.

Authors+Show Affiliations

Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Kuopio, Finland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18394026

Citation

Oikari, S, et al. "Effect of Medium- and Long-chain Fatty Acid Diets On PPAR and SREBP-1 Expression and Glucose Homeostasis in ACBP-overexpressing Transgenic Rats." Acta Physiologica (Oxford, England), vol. 194, no. 1, 2008, pp. 57-65.
Oikari S, Ahtialansaari T, Huotari A, et al. Effect of medium- and long-chain fatty acid diets on PPAR and SREBP-1 expression and glucose homeostasis in ACBP-overexpressing transgenic rats. Acta Physiol (Oxf). 2008;194(1):57-65.
Oikari, S., Ahtialansaari, T., Huotari, A., Kiehne, K., Fölsch, U. R., Wolffram, S., Jänne, J., Alhonen, L., & Herzig, K. H. (2008). Effect of medium- and long-chain fatty acid diets on PPAR and SREBP-1 expression and glucose homeostasis in ACBP-overexpressing transgenic rats. Acta Physiologica (Oxford, England), 194(1), 57-65. https://doi.org/10.1111/j.1748-1716.2008.01860.x
Oikari S, et al. Effect of Medium- and Long-chain Fatty Acid Diets On PPAR and SREBP-1 Expression and Glucose Homeostasis in ACBP-overexpressing Transgenic Rats. Acta Physiol (Oxf). 2008;194(1):57-65. PubMed PMID: 18394026.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of medium- and long-chain fatty acid diets on PPAR and SREBP-1 expression and glucose homeostasis in ACBP-overexpressing transgenic rats. AU - Oikari,S, AU - Ahtialansaari,T, AU - Huotari,A, AU - Kiehne,K, AU - Fölsch,U R, AU - Wolffram,S, AU - Jänne,J, AU - Alhonen,L, AU - Herzig,K-H, Y1 - 2008/04/03/ PY - 2008/4/9/pubmed PY - 2008/10/4/medline PY - 2008/4/9/entrez SP - 57 EP - 65 JF - Acta physiologica (Oxford, England) JO - Acta Physiol (Oxf) VL - 194 IS - 1 N2 - AIM: Acyl-CoAs are important intermediates and regulators of lipid metabolism. Binding proteins like acyl-CoA binding protein (ACBP) can influence their regulatory functions. ACBP has also been shown to exert direct effects on gene regulation in vitro. As the physiological relevance of ACBP in the regulation of lipid metabolism under high fat diets is unclear, we investigated the influence of such diets on the metabolic responses in ACBP-overexpressing rats. METHODS: A transgenic rat line overexpressing the ACBP gene was used to study the effects of 4 weeks of feeding with medium- (MC) or long-chain (LC) fatty acid-containing diets. Glucose tolerance tests were performed. Expression of transcription factors was measured by quantitative RT-PCR and protein levels of AMP-activated protein kinase were determined by western blotting. RESULTS: Transgenic animals fed the MC diet had an improved glucose tolerance and lower serum insulin levels compared with controls. Their liver PPARgamma (by 43%) and SREBP-1 (by 35%) mRNA levels were found to be decreased, while adipose tissue PPARgamma expression was increased by 31%. Tg animals fed the LC diet did not exhibit changes in glucose or insulin levels but exhibited increased mRNA levels of liver PPARs and SREBP-1 (1.5-3.5 times) and decreased protein levels of AMPKalpha (by 48%). CONCLUSIONS: Our results demonstrate that ACBP overexpression affects metabolic responses to diets with distinct difference in their fatty acid chain lengths. The molecular regulatory mechanism behind these effects seems to be an ACBP-induced tissue-specific regulation of expression of PPARs and SREBP. SN - 1748-1716 UR - https://www.unboundmedicine.com/medline/citation/18394026/Effect_of_medium__and_long_chain_fatty_acid_diets_on_PPAR_and_SREBP_1_expression_and_glucose_homeostasis_in_ACBP_overexpressing_transgenic_rats_ L2 - https://doi.org/10.1111/j.1748-1716.2008.01860.x DB - PRIME DP - Unbound Medicine ER -