DGAT2
Diacylglycerol O-acyltransferase 2 (EC 2.3.1.20) (Acyl-CoA retinol O-fatty-acyltransferase) (EC 2.3.1.76) (ARAT) (Retinol O-fatty-acyltransferase) (Diglyceride acyltransferase 2) [HMFN1045] [UNQ738/PRO1433]
Publications[править]
In aging, the capacity of subcutaneous adipose tissue (SAT) to store lipids decreases and this results in metabolically unfavorable fat redistribution. Triggers of this age-related SAT dysfunction may include cellular senescence or endoplasmic reticulum (ER) stress. Therefore, we compared lipogenic capacity of SAT between young and older women and investigated its relation to senescence and ER stress markers. Samples of SAT and corresponding SAT-derived primary preadipocytes were obtained from two groups of women differing in age (36 vs. 72 years, n = 15 each) but matched for fat mass. mRNA levels of selected genes (lipogenesis: ACACA, FASN, SCD1, DGAT2, ELOVL6; senescence: p16, p21, NOX4, GDF15; ER stress-ATF4, XBP1s, PERK, HSPA5, GADD34, HYOU1, CHOP, EDEM1, DNAJC3) were assessed by qPCR, protein levels of GDF15 by ELISA, and mitochondrial function by the Seahorse Analyzer. Compared to the young, SAT and in vitro differentiated adipocytes from older women exhibited reduced mRNA expression of lipogenic enzymes. Out of analyzed senescence and ER stress markers, the only gene, whose expression correlated negatively with the expression of lipogenic enzymes in both SAT and adipocytes, was GDF15, a marker of not only senescence but also mitochondrial dysfunction. In line with this, inhibition of mitochondrial ATP synthase in adipocytes strongly upregulated GDF15 while reduced expression of lipogenic enzymes. Moreover, adipocytes from older women had a tendency for diminished mitochondrial capacity. Thus, a reduced lipogenic capacity of adipocytes in aged SAT appears to be linked to mitochondrial dysfunction rather than to ER stress or accumulation of senescent cells.
MeSH Terms
- Adipocytes
- Adult
- Aged
- Aging
- Biomarkers
- Cell Differentiation
- Cellular Senescence
- Endoplasmic Reticulum Stress
- Female
- Growth Differentiation Factor 15
- Humans
- Lipogenesis
- Mitochondria
- Subcutaneous Fat
Keywords
- Aging
- Lipogenesis
- Mitochondrial dysfunction
- Senescence
- Stress of endoplasmic reticulum
- Subcutaneous adipose tissue
Aged male rats show a decrease in liver PPARalpha. We aimed to determine if the sexual dimorphism in lipid metabolism observed in the PPARalpha-/- mouse is also present in senescent rats. Eighteen-month old rats were obese and presented high plasma NEFA concentrations. Old male rats were more hypercholesterolemic and hyperleptinemic than females, presenting a higher content in hepatic triglycerides and cholesteryl esters, while 18-month old females were more hypertriglyceridemic than males. Although PPARalpha expression and binding activity was reduced in liver from old male and female rats, the mRNA for a PPARalpha target gene, such as CPT-I, was reduced in old males (-56%), while increased by 286% in old females. LXRalpha protein was increased, and its binding activity was decreased in livers of old males, while livers of old females showed an increase in DGAT1 (2.6-fold) and DGAT2 (4.9-fold) mRNA, with respect to 3-month old animals. The increases in DGAT1 and DGAT2 mRNAs matched in old females those of plasma (3.1-fold) and liver triglycerides (5.0-fold). These features disclose a marked sexual dimorphism in lipid metabolism associated to old age in rats that can be partially attributed not only to an age-related decrease in liver PPARalpha expression, but also to changes in other hepatic transcription factors and enzymes, such as liver X receptor alpha (LXRalpha) and diacylglycerol acyltransferases (DGAT).
MeSH Terms
- Acyltransferases
- Aging
- Animals
- Diacylglycerol O-Acyltransferase
- Electrophoretic Mobility Shift Assay
- Female
- Gene Expression Regulation, Enzymologic
- Hormones
- Lipid Metabolism
- Liver
- Male
- PPAR alpha
- Phenotype
- Rats
- Rats, Sprague-Dawley
- Sex Characteristics