| First Author | Guo X | Year | 2023 |
| Journal | Metabolism | Volume | 144 |
| Pages | 155564 | PubMed ID | 37088120 |
| Mgi Jnum | J:337235 | Mgi Id | MGI:7470566 |
| Doi | 10.1016/j.metabol.2023.155564 | Citation | Guo X, et al. (2023) Loss of APOO (MIC26) aggravates obesity-related whitening of brown adipose tissue via PPARalpha-mediated functional interplay between mitochondria and peroxisomes. Metabolism 144:155564 |
| abstractText | BACKGROUND: Mitochondrial dysfunction and aberrant structure in adipose tissue occur in obesity and obesity-linked brown adipose tissue (BAT) whitening; however, whether this aberrant architecture contributes to or is the result of obesity is unknown. Apolipoprotein O (APOO) is a constitutive protein of the mitochondrial cristae organizing system complex. This study aimed to characterize the physiological consequences of APOO deficiency in vivo. METHODS: APOO expression was analyzed in different human and murine adipose depots, and mice lacking APOO in adipocytes (Apoo(ACKO)) are developed to examine the metabolic consequences of adipocyte-specific APOO ablation in vitro and in vivo. RESULTS: Results showed that APOO expression is reduced in BAT from both diet-induced and leptin-deficient obese mice. APOO-knockout mice showed increased adiposity, BAT dysfunction and whitening, reduced non-shivering thermogenesis, and blunted responses to cold stimuli. APOO deficiency disrupted mitochondrial structure in brown adipocytes and impaired oxidative phosphorylation, thereby inducing a shift from oxidative to glycolytic metabolism, increasing lipogenic enzyme levels and BAT whitening. APOO inactivation inhibited thermogenesis in BAT by reducing mitochondrial long-chain fatty acid oxidation. It also disturbed peroxisomal biogenesis and very long-chain fatty acid oxidation via peroxisome proliferator-activated receptor alpha. CONCLUSIONS: Altogether, APOO deficiency in adipocytes aggravates BAT whitening and diet-induced obesity; thus, APOO could be a therapeutic target for obesity. |
