A fat- and sucrose-enriched diet causes metabolic alterations in mdx mice
Date
2023-11-15
Authors
Krishna, Swathy
Echevarria, Kenneth G.
Reed, Carter H.
Eo, Hyeyoon
Wintzinger, Michelle
Quattrocelli, Mattia
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American Physiological Society
Abstract
Duchenne muscular dystrophy (DMD), a progressive muscle disease caused by the absence of functional dystrophin protein, is associated with multiple cellular, physiological, and metabolic dysfunctions. As an added complication to the primary insult, obesity/insulin resistance (O/IR) is frequently reported in patients with DMD; however, how IR impacts disease severity is unknown. We hypothesized a high-fat, high-sucrose diet (HFHSD) would induce O/IR, exacerbate disease severity, and cause metabolic alterations in dystrophic mice. To test this hypothesis, we treated 7-wk-old mdx (disease model) and C57 mice with a control diet (CD) or an HFHSD for 15 wk. The HFHSD induced insulin resistance, glucose intolerance, and hyperglycemia in C57 and mdx mice. Of note, mdx mice on CD were also insulin resistant. In addition, visceral adipose tissue weights were increased with HFHSD in C57 and mdx mice though differed by genotype. Serum creatine kinase activity and histopathological analyses using Masson’s trichrome staining in the diaphragm indicated muscle damage was driven by dystrophin deficiency but was not augmented by diet. In addition, markers of inflammatory signaling, mitochondrial abundance, and autophagy were impacted by disease but not diet. Despite this, in addition to disease signatures in CD-fed mice, metabolomic and lipidomic analyses demonstrated a HFHSD caused some common changes in C57 and mdx mice and some unique signatures of O/IR within the context of dystrophin deficiency. In total, these data revealed that in mdx mice, 15 wk of HFHSD did not overtly exacerbate muscle injury but further impaired the metabolic status of dystrophic muscle.
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This article is published as Krishna, Swathy, Kenneth G. Echevarria, Carter H. Reed, Hyeyoon Eo, Michelle Wintzinger, Mattia Quattrocelli, Rudy J. Valentine, and Joshua T. Selsby. "A fat-and sucrose-enriched diet causes metabolic alterations in mdx mice." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 325 (2023): R692-R711. doi:https://doi.org/10.1152/ajpregu.00246.2022.
© 2023 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0.
© 2023 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0.