Citrate synthase (CS) is a key mitochondrial compound. The point of this investigation was to test the speculation that low CS movement debilitates the metabolic strength of mice took care of a high fat eating routine (HFD) and advances palmitate-actuated lipotoxicity in muscle cells. C57BL/6J (B6) mice and congenic B6.A-(rs3676616-D10Utsw1)/KjnB6 (B6.A), a strain which conveys the A/J allele of CS on the B6 strain foundation, were taken care of HFD (45% kcal from fat) for 12 weeks. C2C12 mouse muscle cells were utilized to research impacts of CS knockdown on cell practicality and motioning after brooding in 0.8 mM palmitate. CS action, yet not that of β-hydroxyacyl-coenzyme-A dehydrogenase was lower in the gastrocnemius muscle and heart of B6.A mice contrasted with B6 mice (). During HFD taking care of, glucose resilience of mice diminished logically and to a more noteworthy degree in B6.A females contrasted with B6 females, with guys demonstrating a comparative pattern. Body weight and fat increase didn't contrast somewhere in the range of B6.A and B6 mice. After a 18 h hatching in 0.8 mM palmitate C2C12 muscle cells with ∼50% shRNA interceded decrease in CS movement indicated lower () suitability and expanded () levels of cut caspase-3 contrasted with the scramble shRNA rewarded C2C12 cells. A/J strain variation of CS is related with low compound movement and disabled metabolic wellbeing. This could be because of disabled lipid digestion in muscle cells.