Abstract
Objective
The mechanism for different susceptibilities to obesity after short-term high-fat
diet (HFD) feeding is largely unknown. Given the close association between obesity
occurrence and mitochondrial dysfunction, the early events in skeletal muscle mitochondrial
adaptations between HFD-induced obesity (DIO) and HFD-induced obesity resistant (DIO-R)
lean phenotype under excess nutritional environment were explored.
Methods
ICR/JCL male mice were randomly divided into 2 groups, as follows: low-fat diet (LFD)
and HFD groups. After 6 weeks on HFD, HFD-fed mice were classified as DIO or DIO-R
according to their body weight gain. Serum parameters, oxidative stress biomarkers,
the activation of AMPK/ACC axis, and the expression profiles of mitochondrial biogenesis
were measured by using corresponding methods among the LFD control, DIO, and DIO-R
groups.
Results
Serum glucose, total cholesterol, low-density lipoprotein, and high-density lipoprotein
levels were significantly increased in DIO and DIO-R mice compared with LFD controls.
However, DIO-R mice had significantly higher MDA levels and exhibited a significantly
higher level of AMP-activated protein kinase (AMPK) activation and acetyl-CoA carboxylase
(ACC) inactivation than DIO mice. Furthermore, the transcript and protein levels of
transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) coactivator
1α (PGC-1α) and estrogen-related receptor-α (ERRα) in DIO-R mice were significantly
up-regulated compared with the DIO mice.
Conclusions
Although the body weight gain differed, the DIO and DIO-R mice had similar metabolic
disturbance of glucose and lipids after short-term HFD consumption. The diverse alterations
on fatty acid oxidation and mitochondrial biogenesis pathway induced by AMPK activation
might be involved in different susceptibilities to obesity when consuming HFD.
Key words
high-fat diet-induced obesity - high-fat diet-induced obesity resistance - fatty acid
oxidation - mitochondrial biogenesis
