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1.
PLoS Biol ; 19(5): e3000988, 2021 05.
Article in English | MEDLINE | ID: mdl-33979328

ABSTRACT

Although visceral adipocytes located within the body's central core are maintained at approximately 37°C, adipocytes within bone marrow, subcutaneous, and dermal depots are found primarily within the peripheral shell and generally exist at cooler temperatures. Responses of brown and beige/brite adipocytes to cold stress are well studied; however, comparatively little is known about mechanisms by which white adipocytes adapt to temperatures below 37°C. Here, we report that adaptation of cultured adipocytes to 31°C, the temperature at which distal marrow adipose tissues and subcutaneous adipose tissues often reside, increases anabolic and catabolic lipid metabolism, and elevates oxygen consumption. Cool adipocytes rely less on glucose and more on pyruvate, glutamine, and, especially, fatty acids as energy sources. Exposure of cultured adipocytes and gluteal white adipose tissue (WAT) to cool temperatures activates a shared program of gene expression. Cool temperatures induce stearoyl-CoA desaturase-1 (SCD1) expression and monounsaturated lipid levels in cultured adipocytes and distal bone marrow adipose tissues (BMATs), and SCD1 activity is required for acquisition of maximal oxygen consumption at 31°C.


Subject(s)
Adipocytes, White/metabolism , Body Temperature Regulation/physiology , Adaptation, Physiological , Adipocytes/metabolism , Adipocytes/physiology , Adipocytes, Brown/metabolism , Adipocytes, White/physiology , Adipose Tissue/metabolism , Adipose Tissue, White/metabolism , Animals , Cold Temperature , Fatty Acids/metabolism , Female , Lipid Metabolism/physiology , Male , Mice , Mice, Inbred C57BL , Oxygen Consumption , Rats , Rats, Sprague-Dawley , Stearoyl-CoA Desaturase/metabolism
2.
Life Sci ; 239: 116897, 2019 Dec 15.
Article in English | MEDLINE | ID: mdl-31644894

ABSTRACT

AIMS: Lansoprazole (LPZ) is one of the most commonly prescribed drugs for treatment of acid-related diseases, and it is increasingly recognized for its potential application as an anti-diabetic therapy. Although LPZ target tissues remain poorly understood, possible sites of action include adipose tissue. In this study, we assessed effects of LPZ on adipocyte differentiation and function by using 3T3-L1 preadipocytes and HFD-induced obesity mice as an in vitro and in vivo model, respectively. MAIN METHODS: Oil red O staining and intracellular triacylglycerol content were used to determine lipid accumulation. Glucose uptake was performed to measure mature adipocyte function. Expression of adipocyte genes was determined by qRT-PCR and immunoblotting. KEY FINDINGS: LPZ has dual effects on differentiation of 3T3-L1 cells. At low concentrations, LPZ enhanced adipocyte differentiation via induction of PPARγ and C/EBPα, two master adipogenic transcription factors, as well as lipogenic proteins, ACC1 and FASN. Increasing of adipocyte number subsequently increased basal and insulin-stimulated glucose uptake, and expression of Glut4 mRNA. Conversely, high concentrations of LPZ strongly inhibited differentiation and expression of PPARγ and C/EBPα, and maintained expression of preadipocytes markers, ß-catenin and Pref-1. Inhibition of adipogenesis by LPZ reduced mature adipocyte number, Glut4 mRNA expression and insulin-stimulated glucose uptake. In addition, treatment with LPZ at 200 mg/kg significantly reduced body weight gain and total fat mass in HFD-induced obese mice. SIGNIFICANCE: These results indicate that effects of LPZ on adipocyte differentiation are dependent on concentration and are correlated with PPARγ and C/EBPα.


Subject(s)
Adipocytes/drug effects , Adipocytes/metabolism , Lansoprazole/metabolism , 3T3-L1 Cells , Adipocytes/physiology , Adipogenesis/drug effects , Animals , CCAAT-Enhancer-Binding Protein-alpha/metabolism , Cell Differentiation/drug effects , Diet, High-Fat , Glucose Transporter Type 4/metabolism , Insulin/metabolism , Lansoprazole/pharmacology , Lipid Metabolism/drug effects , Lipogenesis , Male , Mice , Mice, Inbred C57BL , Obesity/metabolism , PPAR gamma/metabolism , Triglycerides/metabolism
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