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Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet.
Am J Physiol Endocrinol Metab. 2007 Jul; 293(1):E121-31.AJ

Abstract

To determine whether long-term melanocortinergic activation can attenuate the metabolic effects of a high fat diet, mice overexpressing an NH(2)-terminal POMC transgene that includes alpha- and gamma(3)-MSH were studied on either a 10% low-fat diet (LFD) or 45% high-fat diet (HFD). Weight gain was modestly reduced in transgenic (Tg-MSH) male and female mice vs. wild type (WT) on HFD (P < 0.05) but not LFD. Substantial reductions in body fat percentage were found in both male and female Tg-MSH mice on LFD (P < 0.05) and were more pronounced on HFD (P < 0.001). These changes occurred in the absence of significant feeding differences in most groups, consistent with effects of Tg-MSH on energy expenditure and partitioning. This is supported by indirect calorimetry studies demonstrating higher resting oxygen consumption and lower RQ in Tg-MSH mice on the HFD. Tg-MSH mice had lower fasting insulin levels and improved glucose tolerance on both diets. Histological and biochemical analyses revealed that hepatic fat accumulation was markedly reduced in Tg-MSH mice on the HFD. Tg-MSH also attenuated the increase in corticosterone induced by the HFD. Higher levels of Agrp mRNA, which might counteract effects of the transgene, were measured in Tg-MSH mice on LFD (P = 0.02) but not HFD. These data show that long-term melanocortin activation reduces body weight, adiposity, and hepatic fat accumulation and improves glucose metabolism, particularly in the setting of diet-induced obesity. Our results suggest that long-term melanocortinergic activation could serve as a potential strategy for the treatment of obesity and its deleterious metabolic consequences.

Authors+Show Affiliations

Department of Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17374695

Citation

Lee, Michelle, et al. "Transgenic MSH Overexpression Attenuates the Metabolic Effects of a High-fat Diet." American Journal of Physiology. Endocrinology and Metabolism, vol. 293, no. 1, 2007, pp. E121-31.
Lee M, Kim A, Chua SC, et al. Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet. Am J Physiol Endocrinol Metab. 2007;293(1):E121-31.
Lee, M., Kim, A., Chua, S. C., Obici, S., & Wardlaw, S. L. (2007). Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet. American Journal of Physiology. Endocrinology and Metabolism, 293(1), E121-31.
Lee M, et al. Transgenic MSH Overexpression Attenuates the Metabolic Effects of a High-fat Diet. Am J Physiol Endocrinol Metab. 2007;293(1):E121-31. PubMed PMID: 17374695.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet. AU - Lee,Michelle, AU - Kim,Andrea, AU - Chua,Streamson C,Jr AU - Obici,Silvana, AU - Wardlaw,Sharon L, Y1 - 2007/03/20/ PY - 2007/3/22/pubmed PY - 2007/9/14/medline PY - 2007/3/22/entrez SP - E121 EP - 31 JF - American journal of physiology. Endocrinology and metabolism JO - Am. J. Physiol. Endocrinol. Metab. VL - 293 IS - 1 N2 - To determine whether long-term melanocortinergic activation can attenuate the metabolic effects of a high fat diet, mice overexpressing an NH(2)-terminal POMC transgene that includes alpha- and gamma(3)-MSH were studied on either a 10% low-fat diet (LFD) or 45% high-fat diet (HFD). Weight gain was modestly reduced in transgenic (Tg-MSH) male and female mice vs. wild type (WT) on HFD (P < 0.05) but not LFD. Substantial reductions in body fat percentage were found in both male and female Tg-MSH mice on LFD (P < 0.05) and were more pronounced on HFD (P < 0.001). These changes occurred in the absence of significant feeding differences in most groups, consistent with effects of Tg-MSH on energy expenditure and partitioning. This is supported by indirect calorimetry studies demonstrating higher resting oxygen consumption and lower RQ in Tg-MSH mice on the HFD. Tg-MSH mice had lower fasting insulin levels and improved glucose tolerance on both diets. Histological and biochemical analyses revealed that hepatic fat accumulation was markedly reduced in Tg-MSH mice on the HFD. Tg-MSH also attenuated the increase in corticosterone induced by the HFD. Higher levels of Agrp mRNA, which might counteract effects of the transgene, were measured in Tg-MSH mice on LFD (P = 0.02) but not HFD. These data show that long-term melanocortin activation reduces body weight, adiposity, and hepatic fat accumulation and improves glucose metabolism, particularly in the setting of diet-induced obesity. Our results suggest that long-term melanocortinergic activation could serve as a potential strategy for the treatment of obesity and its deleterious metabolic consequences. SN - 0193-1849 UR - https://www.unboundmedicine.com/medline/citation/17374695/Transgenic_MSH_overexpression_attenuates_the_metabolic_effects_of_a_high_fat_diet_ L2 - http://www.physiology.org/doi/full/10.1152/ajpendo.00555.2006?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -