Published online May 15, 2024. doi: 10.4239/wjd.v15.i5.988
Peer-review started: December 31, 2023
First decision: January 17, 2024
Revised: January 26, 2024
Accepted: March 11, 2024
Article in press: March 11, 2024
Published online: May 15, 2024
Processing time: 131 Days and 6.4 Hours
The prevalence of visceral obesity among adolescents and young adults is surging, significantly heightening their risk of metabolic diseases, such as type 2 diabetes. While estrogen [17β-estradiol (E2)] is known to offer protection against obesity through diverse mechanisms, its specific impact on visceral adipose tissue (VAT) remains to be fully elucidated.
To investigate the impact of E2 on the gene expression profile within VAT of late pubertal prediabetic mice.
To elucidate the local and direct effects of E2 on VAT and uncover the underlying molecular mechanisms in a prediabetic mouse model.
Female C57BL/6 mice were used to create an E2 deficient prediabetes model through ovariectomy (OVX) followed by high-fat diet (HFD) feeding. Metabolic parameters were monitored. Gene expression profiles in VAT were assessed using Whole Mouse Genome Oligo Microarray. Pathway analyses were conducted with the Kyoto Encyclopedia of Genes and Genomes. Expression of key lipid metabolic genes was confirmed by RT-PCR. Morphological alterations in VAT were examined via HE staining.
HFD modestly elevated the weights of visceral (VAT) and subcutaneous adipose tissue (SAT), a testament to the protective role of endogenous E2. In stark contrast, OVX markedly boosted VAT weight and the VAT/SAT weight ratio, effects that were mitigated by subsequent E2 treatment. OVX led to the down-regulation of genes implicated in both fatty acid biosynthesis and oxidation, signaling a comprehensive slowdown in lipid metabolism. Remarkably, E2 treatment fully reversed these alterations.
OVX intensified the visceral adiposity triggered by HFD feeding, leading to a universally diminished lipid metabolism in the absence of E2. Treatment with E2 effectively reversed this condition, shedding light on the mechanistic insights and the therapeutic promise of E2 in combating visceral obesity.
Mitochondria play a pivotal role in fatty acid elongation and oxidation. Investigating the influence of E2 on mitochondrial fatty acid metabolism is therefore crucial.