Excessive dietary saturated fat or fructose and their combination (found in ultra-processed foods) impair mitochondrial dynamics markers and cause brown adipocyte whitening in adult mice

Abstract

Objective: To investigate the effects of comparable dietary excess of fat or fructose and the combination of these two insults (mimicking ultra-processed foods) on interscapular brown adipose tissue (iBAT) whitening and markers of mitochondrial dynamics in adult male mice.

Methods: Male C57BL/6 mice were randomly assigned into four groups according to the diet: control diet (C, following AIN-93M), high-fat diet (HF, 32% energy as lard), high-fructose diet (HFRU, 32% energy as fructose) or for high-fat/high-fructose diet (HF-HFRU, 32% as lard and 32% as fructose) for 12 weeks. Data were tested with one-way ANOVA and Dunnet T3 post-test (n=5 per analysis, significance level P < 0.05).

Results: All diets caused insulin resistance and iBAT whitening, albeit with overweight only in the HF and HF-HFRU groups. Principal component analysis indicated that the HFRU scores loaded next to inflammation (Nlrp3) and adipogenesis markers (Pparg), and the HF diet influenced more a mitochondrial gene (Tomm20). However, iBAT whitening in all groups was associated with deficits in mitochondrial dynamics (Ppargc1a, Dnml1, and Pink1), vascularization (Vegfa), and thermogenic markers (Bmp8b, and Ucp1).

Conclusion: Similar increases in dietary saturated fat or fructose (32% as energy) and the combination of these two insults (32% / 32%) caused insulin resistance and brown adipocyte dysfunction (whitening) in adult mice after 12 weeks independent of being overweight. In comparison, the PC scores of the HFRU groups were closer to the HF-HFRU group than the HF group, implying a worse outcome and highlighting the importance of limiting saturated fat and fructose intake from ultra-processed foods.

Keywords: Brown adipose tissue; Fructose; Mitochondria; Saturated fat; Whitening.