Differential effects of high fat diet-induced obesity on oocyte mitochondrial functions in inbred and outbred mice

Abstract

Maternal obesity can cause reduced oocyte quality and subfertility. Mitochondrial dysfunction plays a central role here, and most often inbred mouse models are used to study these pathways. We hypothesized that the mouse genetic background can influence the impact of high fat diet (HFD)-induced obesity on oocyte quality. We compared the inbred C57BL/6 (B6) and the outbred Swiss strains after feeding a HFD for 13w. HFD-mice had increased body weight gain, hypercholesterolemia, and increased oocyte lipid droplet (LD) accumulation in both strains. LD distribution was strain-dependent. In Swiss mouse oocytes, HFD significantly increased mitochondrial inner membrane potential (MMP), reactive oxygen species concentrations, mitochondrial ultrastructural abnormalities (by 46.4%), and endoplasmic reticulum (ER) swelling, and decreased mtDNA copy numbers compared with Swiss controls (P < 0.05). Surprisingly, B6-control oocytes exhibited signs of cellular stress compared to the Swiss controls (P < 0.05); upregulated gene expression of ER- and oxidative stress markers, high mitochondrial ultrastructural abnormalities (48.6%) and ER swelling. Consequently, the HFD impact on B6 oocyte quality was less obvious, with 9% higher mitochondrial abnormalities, and no additive effect on MMP and stress marks compared to B6 control (P > 0.1). Interestingly, mtDNA in B6-HFD oocytes was increased suggesting defective mitophagy. In conclusion, we show evidence that the genetic background or inbreeding can affect mitochondrial functions in oocytes and may influence the impact of HFD on oocyte quality. These results should create awareness when choosing and interpreting data obtained from different mouse models before extrapolating to human applications.

Adipose triglyceride lipase promotes prostaglandin-dependent actin remodeling by regulating substrate release from lipid droplets

“…Indeed, LD accumulation, composition, and localization are dynamic during oocyte maturation [4, 12], LDs are hubs for FA trafficking, and FA levels (including that of AA) are critical for oocyte development in many species [7, 13, 105]. Further, in both mouse models and human patients, metabolic syndrome causes LD clustering in oocytes, failures in oocyte maturation, and decreased fertility [13–15, 106, 107]. But does this relate to PG signaling?…”

Oleoylethanolamide Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in High-Fat Diet-Fed Rats

“…The pathways for ROS production and oxidative stress have been reported to be upregulated in the liver of mice consuming an HFD, and this event precedes the onset of insulin resistance [12]. Moreover, both animal and human studies have reported that longterm HFD feeding leads to increased oxidative stress and dysfunctional mitochondria in many organs [13][14][15][16] and induces ER stress in vitro [6][7][8][9]. The functional crosstalk between oxidative stress and ER stress is well described.…”

Diet normalization or caloric restriction as a preconception care strategy to improve metabolic health and oocyte quality in obese outbred mice

“…Oocytes, collected from obese patients but also from Western Type diet induced obese mice, displayed an impaired quality, indicated by high rates of meiotic spindle abnormalities, increased mitochondrial ultrastructural abnormalities, altered mitochondrial membrane potential and increased cellular oxidative stress levels [ 16 – 19 ]. Furthermore, mitochondrial DNA (mtDNA) copy number and mitochondrial biogenesis in oocytes from obese mice were altered [ 18 ] and higher levels of lipid accumulation and abnormal lipid distribution in oocytes were present [ 18 – 20 ].…”