Acetyl-CoA Regulation, OXPHOS Integrity and Leptin Levels Are Different in Females With Childhood vs Adulthood Onset of Obesity
| Autor: | Natalie Khor, Jessica Murphy, Bjorn T. Tam, Jose A. Morais, Sylvia Santosa |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Leptin Male medicine.medical_specialty ATP citrate lyase Adipose tissue 030209 endocrinology & metabolism Oxidative phosphorylation Oxidative Phosphorylation Pathogenesis 03 medical and health sciences Sex Factors 0302 clinical medicine Endocrinology Acetyl Coenzyme A Internal medicine medicine Humans Obesity Age of Onset Child Histone H3 acetylation 030304 developmental biology 0303 health sciences Adiponectin Chemistry Age Factors 3. Good health Adipose Tissue Body Composition Female NAD+ kinase Oxidation-Reduction |
| Zdroj: | Endocrinology. 161 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endocr/bqaa142 |
| Popis: | Although childhood-onset obesity (CO) and adulthood-onset obesity (AO) are known to lead to distinctive clinical manifestations and disease risks, the fundamental differences between them are largely unclear. The aim of the current study is to investigate the fundamental differences between subcutaneous adipose tissue from CO and AO and to identify metabolic differences between abdominal (abSAT) and femoral subcutaneous adipose tissues (feSAT). Total and regional body composition was assessed using dual-energy x-ray absorptiometry (DXA) and computed tomography. Levels of acetyl-CoA, NAD+/NADH, acetyl-CoA network genes, mitochondrial complex abundance, H3 acetylation were determined in biopsied abSAT and feSAT. Serum leptin and adiponectin were measured. Our results showed that acetyl-CoA was higher in subcutaneous adipose tissue from subjects with AO compared with CO. Multiple linear regression revealed that ATP citrate lyase was the only main effect affecting the level of acetyl-CoA. Circulating leptin concentrations was higher in AO. The increased level of acetyl-CoA was strongly associated with histone H3 acetylation, LEP expression in adipose tissue, and circulating leptin in AO. NAD+/NADH was higher in CO; however, abundance of mitochondrial complexes, the complex II:complex V ratio, and the complex IV:complex V ratio were lower in CO, reflecting compromised mitochondrial function in subcutaneous adipose tissue from CO. Moreover, we identified differences in the level of acetyl-CoA and NAD+/NADH ratio between abSAT and feSAT, suggesting that these fat depots may possess different metabolic properties. The fundamental difference in the important metabolic intermediate acetyl-CoA between CO and AO may help us better understand the development of obesity and the pathogenesis of different obesity-related diseases in humans. |
| Databáze: | OpenAIRE |
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