17β-estradiol improves hepatic mitochondrial biogenesis and function through PGC1B.

Area of Science:

• * Endocrinology
• * Cellular Biology
• * Metabolism

Background:

• * Sexual dimorphism impacts mitochondrial biogenesis and function across rat tissues.
• * Female rats exhibit larger, more functional mitochondria.
• * Peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) family members regulate mitochondrial processes, with limited understanding of hepatic PGC1A and PGC1B roles.

Purpose of the Study:

• * To investigate the role of 17β-estradiol (E2) in liver mitochondrial biogenesis and function.
• * To determine the contribution of hepatic PGC1A and PGC1B in mediating E2's effects.
• * To elucidate the protective mechanisms of E2 in hepatocytes.

Main Methods:

• * Ovariectomized (OVX) rat model with and without E2 treatment.
• * In vitro studies using HepG2 hepatocytes.
• * Gene knockdown experiments using small interfering RNA (siRNA) targeting PGC1A and PGC1B.

Main Results:

• * Estrogen deficiency in OVX rats impaired mitochondrial biogenesis, function, and lipid metabolism, increasing oxidative stress.
• * E2 treatment counteracted these negative effects.
• * In HepG2 cells, E2 enhanced mitochondrial biogenesis and function; these effects were independent of PGC1A but dependent on PGC1B.
• * Knockdown of PGC1B significantly impaired E2's beneficial effects on hepatocyte mitochondria.

Conclusions:

• * 17β-estradiol (E2) exerts widespread protective effects in hepatocytes by enhancing mitochondrial content, oxidative capacity, and reducing lipid accumulation and oxidative stress.
• * Hepatic PGC1B acts as a novel mediator of E2's effects on mitochondrial biogenesis and function.
• * PGC1B activation presents a potential therapeutic strategy for managing hepatic mitochondrial disorders.