Certain individuals ingesting a low-fat diet are still prone to visceral obesity, and the reasons remain undetermined. This study aimed to investigate differentially expressed proteins of visceral adipose tissues between low-fat diet-fed obesity-resistant and obesity-prone C57BL/6 mice through a proteomics approach and to ascertain potential mechanisms associated with these obesity-prone animals. First, animals were fed low-fat or normal-chow diets for 6 weeks. Dietary intake and body weight were monitored during this period. After 6 weeks of the low-fat diet, obesity-prone and obesity-resistant mice (NOP and NOR groups) were defined as those within the upper and lower quarters for weight gain, respectively. Proteomic analysis showed that ubiquinol-cytochrome c reductase core protein 1 (Uqcrc1) and Enolase 3, β muscle were decreased by 8.1- and 8.8-fold in the visceral adipose tissues of the NOP mice compared to the NOR controls, respectively, while monoglyceride lipase (MGLL) and glucose-6-phosphate dehydrogenase (G6PDH) X-linked were increased by 5.3- and 4.7-fold, respectively. These results indicate that obesity-prone animals fed low-fat diets exhibited differentially expressed proteins, e.g., Uqcrc1, Enolase 3, MGLL and G6PDH involved in energy metabolism, glycolysis and fat synthesis in visceral adipose tissues, which are useful for defining molecular markers and understanding the mechanisms of the development of obesity.

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