The Effects of a High Fat Diet on Mitochondrial Biogenesis and Inflammation in the Brain.

摘要

INTRO: High fat diets (HFD) ingested over long periods of time have been shown to cause diet induced obesity leading to excessive adiposity and chronic low grade inflammation. Here we have shown how differing levels of saturated fats (SF), which are common storage fats, affect markers of inflammation and mitochondrial biogenesis. IL-1β and TNF-alpha are pro-inflammatory cytokines that have been shown to increase with a HFD, while molecular signalers, PGC-1alpha, cyt c, and SIRT1, related to mitochondrial biogenesis have been shown to decrease. Despite the risks of consuming a diet high in SF's, consumers continue to buy energy dense foods that are well known to cause metabolic dysregulation. METHODS: Male C57BL/6 mice were randomized into groups (n=8/9) (AIN 76 A), (AIN 76 A mod), (6% HFD), (12% HFD), (24% HFD). Mice were fed either HFD or LFD for 16 weeks. Body weights were measured weekly. At 20 weeks of age mice were sacrificed and brain parts (hypothalamus, hippocampus, and cerebellum) were isolated for mRNA analysis of two inflammatory cytokines (IL-1β, TNF-alpha), and three molecular signalers (PGC-1alpha, SIRT1, and cyt c) using QT-PCR. RESULTS: High fat feeding increased the accumulation of mass and obesogenic characteristics. Beginning at 12 weeks of age all HFD groups were different from control (AIN 76 A) (P<0.05). Beginning at 17 weeks of age the 12% HFD group was different from both the 6% and 24% HFD group. Gene expression of cyt c in the cerebellum increased in the 6% HFD relative to control (P < 0.033) and gene expression of IL-1β in the hypothalamus increased in the 12% HFD group relative to control (P <0.031). CONLU: These findings suggest that diets high in saturated fat (6%, 12%, 24%), but the same in total fat (40%) leads to an increase in body weight and obesogenic characteristics, with the largest difference in the 12% HFD group. This was associated with increased IL-1β expression in the hypothalamus, while the 6% HFD was associated with an increase in cyt c expression suggesting changes in mitochondrial biogenesis in the cerebellum.