Browning of white adipose tissue (WAT) is suggested as a promising therapeutic approach to induce energy expenditure and counteract obesity and its associated complications. Systemic depletion of spinophilin (SPL) increases metabolism and improves energy balance in mice. In this study, we explored the mechanistic insight of SPL action in WAT browning. Gene expression and mitochondria tracker staining showed that visceral white adipose tissue (vWAT) harvested from SPL KO mice had a higher expression of classic browning-related genes, including uncoupling protein 1 ( UCP1 ), Cell death inducing DFFA like effector A (CIDEA) and PR domain containing 16 (PRDM16) , as well as a higher mtDNA level compared to vWAT from wild type (WT) control mice. When adipogenesis was induced in pre-adipocytes harvested from KO and WT mice ex vivo using the PPAR-γ agonist rosiglitazone (Rosi), SPL KO cells showed increased browning marker gene expression and mitochondria function compared to cells from WT mice. Increased PPAR-γ protein expression and nucleus retention in vWAT from SPL KO mice after Rosi treatment were also observed. The effect of SPL on vWAT browning was further confirmed in vivo when WT and KO mice were treated with Rosi. As a result, SPL KO mice lost body weight, which was associated with increased expression of browning maker genes in vWAT. In summary, our data demonstrate the critical role of SPL in the regulation of WAT browning.
Keyphrases
- high fat diet induced
- insulin resistance
- adipose tissue
- gene expression
- wild type
- cell death
- high fat diet
- metabolic syndrome
- skeletal muscle
- type diabetes
- poor prognosis
- body weight
- small molecule
- risk factors
- electronic health record
- fatty acid
- high glucose
- physical activity
- protein protein
- newly diagnosed
- endothelial cells
- combination therapy
- endoplasmic reticulum stress
- weight gain
- data analysis
- deep learning
- amino acid
- nitric oxide synthase