Regulation of Mitochondrial and Peroxisomal Metabolism in Female Obesity and Type 2 Diabetes

• Published in: International journal of molecular sciences Vol. 25; no. 20; p. 11237
• Main Authors: Antelo-Cea, Damián A., Martínez-Rojas, Laura, Cabrerizo-Ibáñez, Izan, Roudi Rashtabady, Ayda, Hernández-Alvarez, María Isabel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 19.10.2024; MDPI
• Subjects: Aerobics; Animals; Biosynthesis; Care and treatment; Clinical trials; Complications and side effects; Diabetes; Diabetes Mellitus, Type 2 - metabolism; Enzymes; Estrogens; Estrogens - metabolism; Exercise; Fatty acids; Fatty liver; Female; Females; Global health; Health aspects; Hormone therapy; Humans; Insulin resistance; Lipid Metabolism; Lipids; Liver cirrhosis; Menopause; Metabolic disorders; Metabolic syndrome; Metabolites; Mitochondria; Mitochondria - metabolism; Mitochondrial diseases; Obesity; Obesity - metabolism; Oxidation; Oxidative phosphorylation; Oxidative stress; Patient outcomes; Peroxisome Proliferator-Activated Receptors - metabolism; Peroxisomes - metabolism; Phosphorylation; Physical fitness; Polyamines; Postmenopausal women; Prevention; Review; Risk factors; Womens health; Spain; metabolic disorders; type 2 diabetes; lipid metabolism; estrogens; peroxisomes; insulin resistance; PPARs; obesity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms252011237

Obesity and type 2 diabetes (T2D) are widespread metabolic disorders that significantly impact global health today, affecting approximately 17% of adults worldwide with obesity and 9.3% with T2D. Both conditions are closely linked to disruptions in lipid metabolism, where peroxisomes play a pivotal role. Mitochondria and peroxisomes are vital organelles responsible for lipid and energy regulation, including the β-oxidation and oxidation of very long-chain fatty acids (VLCFAs), cholesterol biosynthesis, and bile acid metabolism. These processes are significantly influenced by estrogens, highlighting the interplay between these organelles’ function and hormonal regulation in the development and progression of metabolic diseases, such as obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), and T2D. Estrogens modulate lipid metabolism through interactions with nuclear receptors, like peroxisome proliferator-activated receptors (PPARs), which are crucial for maintaining metabolic balance. Estrogen deficiency, such as in postmenopausal women, impairs PPAR regulation, leading to lipid accumulation and increased risk of metabolic disorders. The disruption of peroxisomal–mitochondrial function and estrogen regulation exacerbates lipid imbalances, contributing to insulin resistance and ROS accumulation. This review emphasizes the critical role of these organelles and estrogens in lipid metabolism and their implications for metabolic health, suggesting that therapeutic strategies, including hormone replacement therapy, may offer potential benefits in treating and preventing metabolic diseases.