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Genes 2017, 8(11), 307; doi:10.3390/genes8110307

The MXL-3/SBP-1 Axis Is Responsible for Glucose-Dependent Fat Accumulation in C. elegans

1
Laboratorio de Nutrición Experimental, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
2
Unidad de Genética de la Nutrición, Instituto de Investigaciones Biomédicas UNAM - Instituto Nacional de Pediatría, Mexico City 04530, Mexico
3
Laboratorio de Bioquímica Genética, Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
4
Consejo Nacional de Ciencia y Tecnología (CONACYT), Instituto Nacional de Pediatría, Secretaría de Salud, Mexico City 04530, Mexico
*
Author to whom correspondence should be addressed.
Academic Editor: Paolo Cinelli
Received: 6 October 2017 / Revised: 31 October 2017 / Accepted: 31 October 2017 / Published: 6 November 2017
(This article belongs to the Section Molecular Genetics)
View Full-Text   |   Download PDF [3490 KB, uploaded 8 November 2017]   |  

Abstract

Chronic exposure to elevated glucose levels leads to fatty acid accumulation, which promotes the development of metabolic diseases such as obesity and type 2 diabetes. MXL-3 is a conserved transcriptional factor that modulates the inhibition of lipolysis in Caenorhabditis elegans. However, the role of MXL-3 in lipid metabolism during nutrient excess remains unknown. We hypothesized that inhibition of MXL-3 prevents glucose-dependent fat accumulation. Nematodes from wild-type N2, MXL-3::GFP and sbp-1 or mxl-3 null strains were grown on standard, high glucose or high glucose plus metformin plates for 24 h. Using laser-scanning confocal microscopy, we monitored the glucose-induced activation of MXL-3 labeled with GFP (MXL-3::GFP). Lipid levels were determined by Oil Red O (ORO) staining and gas chromatography/mass spectrometry, and gene expression was assessed by qRT-PCR. We found that high glucose activated MXL-3 by increasing its rate of nuclear entry, which in turn increased lipid levels via sterol regulatory element-binding protein (SBP-1). This activated critical genes that synthesize long chain unsaturated fatty acids (MUFAs and PUFAs) and repress lipolytic genes. Interestingly, the anti-diabetic drug metformin inhibited MXL-3 activation and subsequently prevented glucose-dependent fat accumulation. These findings highlight the importance of the MXL-3/SBP-1 axis in the regulation of lipid metabolism during nutritional excess and provide new insight into the mechanism by which metformin prevents lipid accumulation. This study also suggests that inhibition of MXL-3 may serve as a potential target for the treatment of chronic metabolic diseases, including obesity, type 2 diabetes, and cardiovascular disease. View Full-Text
Keywords: Caenorhabditis elegans; glucose; fatty acid; energy metabolism; transcription factor; energy sensor Caenorhabditis elegans; glucose; fatty acid; energy metabolism; transcription factor; energy sensor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Mejia-Martinez, F.; Franco-Juarez, B.; Moreno-Arriola, E.; Hernández-Vázquez, A.; Martinez-Avila, M.; Gómez-Manzo, S.; Marcial-Quino, J.; Carvajal, K.; Velazquez-Arellano, A.; Ortega-Cuellar, D. The MXL-3/SBP-1 Axis Is Responsible for Glucose-Dependent Fat Accumulation in C. elegans. Genes 2017, 8, 307.

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