Adipocyte and Cell Biology

Depot-specific UCP1 expression in human white adipose tissue and its association with obesity-related markers

Abstract

Background

This study investigated depot-specific mRNA expression of uncoupling protein 1 (UCP1) in human white adipose tissue (WAT) and its association with obesity-related markers.

Methods

We recruited 39 normal-weight, 41 nondiabetic obese, and 22 diabetic obese women. We measured UCP1 mRNA expression in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated the associations between UCP1 mRNA expression in VAT and SAT, and obesity-related markers including mRNA expression of leptin, adiponectin, CCAAT-enhancer-binding protein homologous protein (CHOP), and positive regulatory domain-containing protein 16 (PRDM16). We also evaluated UCP1 mRNA expression in differentiated human white adipocytes after treatment with various stressors and metabolic improvement agents in vitro.

Results

UCP1 mRNA in VAT was significantly higher than in SAT in all groups. UCP1 mRNA in SAT was negatively correlated with BMI, total abdominal fat area, visceral fat area, blood pressure, fasting glucose, insulin, HOMA-IR score, triglyceride, hsCRP, fasting leptin levels, and adipocyte size. UCP1 mRNA in SAT was positively correlated with fasting adiponectin levels. UCP1 mRNA in VAT was negatively correlated with visceral-to-subcutaneous fat ratio (VSR), fasting glucose, and triglyceride levels. In SAT, UCP1 mRNA was negatively correlated with mRNA expression of leptin and CHOP, and positively correlated with mRNA expression of adiponectin. The expression of PRDM16 was positively correlated with UCP1 mRNA in both VAT and SAT. UCP1 mRNA expression in differentiated human white adipocytes was significantly reduced after incubation with thapsigargin, tunicamycin, homocysteine, TNF-α, or IL-β, and significantly increased after incubation with exendin 4, dapagliflozin, and telmisartan.

Conclusions

This study demonstrated depot-specific mRNA expression of UCP1 and its association with obesity-related markers in human WAT. UCP1 mRNA in human white adipocytes was suppressed by inflammatory agents and enhanced by metabolic improvement agents. UCP1 in human WAT might participate in the pathogenesis of obesity-related metabolic diseases.

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Fig. 1: UCP1 mRNA expression in the visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) of normal-weight control (n = 39), nondiabetic obese (n = 41), and diabetic obese groups (n = 22).
Fig. 2: Correlation of UCP1 mRNA expression in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) with mRNA expression of insulin sensitivity markers (leptin and adiponectin), ER stress markers (CHOP; CCAAT-enhancer-binding protein homologous protein), and beiging-related markers (PRDM16; positive regulatory domain-containing protein 16) in VAT and SAT (n = 102).
Fig. 3: Changes in UCP1 mRNA expression in human differentiated adipocytes in response to ER stress inducer or proinflammatory cytokine treatment.
Fig. 4: Induction of UCP1 mRNA expression by exendin 4, dapagliflozin, and telmisartan in differentiated human adipocytes.

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Acknowledgements

This study was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2017R1D1A1B03030666) and by the Ministry of Science, ICT and Future Planning (2017R1A2B4008673).

Author information

JL wrote the paper and analyzed the data. HSP and YJJ conceived the idea of the study and reviewed and edited the paper. JK performed experiments and analyzed the data. J-HK and YH provided samples and reviewed the paper. YJL interpreted the data and reviewed the paper. All authors interpreted the data and provided valuable input at all stages. All authors have approved the final version of the article for publication.

Correspondence to Hye Soon Park or Yeon Jin Jang.

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Lim, J., Park, H.S., Kim, J. et al. Depot-specific UCP1 expression in human white adipose tissue and its association with obesity-related markers. Int J Obes 44, 697–706 (2020). https://doi.org/10.1038/s41366-020-0528-4

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