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Research Project: Improved Vegetable Processing Methods to Reduce Environmental Impact, Enhance Product Quality and Reduce Food Waste

Location: Food Science and Market Quality and Handling Research Unit

Title: Biomarkers of metabolic adaptation to high dietary fats in a mouse model of obesity resistance

item MILHEM, FADIA - North Carolina State University
item HAMILTON, LEAH - North Carolina State University
item SKATES, EMILY - North Carolina State University
item WILSON, MICKEY - North Carolina State University
item Johanningsmeier, Suzanne
item KOMARNYTSKY, SLAVKO - North Carolina State University

Submitted to: Metabolites
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/16/2024
Publication Date: 1/20/2024
Citation: Milhem, F., Hamilton, L.M., Skates, E., Wilson, M., Johanningsmeier, S.D., Komarnytsky, S. 2024. Biomarkers of metabolic adaptation to high dietary fats in a mouse model of obesity resistance. Metabolites. 14(1):69.

Interpretive Summary: This study investigated individual obesity resistance in a mouse model, revealing a complex interplay of physiological adaptations that contribute to their phenotype. The distinct metabolic traits observed in the skeletal muscle hint at possible adaptive mechanisms that promote effective lipid utilization and mitigate the associated oxidative stress. Concurrently, the shift in gut microbiota composition and fecal volatile metabolite profiles identified potential volatile biomarkers to monitor the pathophysiology and progression of obese states. Understanding the intricate mechanisms governing resistance to obesity provides valuable insights into metabolic adaptations and unveils potential molecular targets aimed at modulating energy metabolism and mitigating obesity-related complications.

Technical Abstract: Obesity-resistant (non-responder, NR) phenotypes that exhibit reduced susceptibility to developing obesity despite being exposed to high dietary fat are crucial in exploring the metabolic responses that protect against obesity. Although several efforts have been made to study them in mice and humans, the individual protective mechanisms are poorly understood. In this exploratory study, we used a polygenic C57BL/6J mouse model of diet-induced obesity to show that NR mice developed healthier fat/lean body mass ratios (0.43 ± 0.05) versus the obesity-prone (super-responder, SR) phenotypes (0.69 ± 0.07, p < 0.0001) by upregulating gene expression networks that promote the accumulation of type 2a, fast-twitch, oxidative muscle tissues. This was achieved in part by a metabolic adaptation in the form of blood glucose sparing, thus aggravating glucose tolerance. Resistance to obesity in NR mice was associated with 4.9-fold upregulated mitoferrin 1 (Slc25a37), an essential mitochondrial iron importer. SR mice also showed fecal volatile metabolite signatures of enhanced short-chain fatty acid metabolism, including increases in detrimental methyl formate and ethyl propionate, and these effects were reversed in NR mice. Continued research into obesityresistant phenotypes can offer valuable insights into the underlying mechanisms of obesity and metabolic health, potentially leading to more personalized and effective approaches for managing weight and related health issues.