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Endocrine Abstracts (2019) 65 P185 | DOI: 10.1530/endoabs.65.P185

SFEBES2019 POSTER PRESENTATIONS Metabolism and Obesity (104 abstracts)

Endotoxin and adiposity as mediators of down-regulating the BRITE fat phenotype

Farah Omran 1 , Alice Murphy 2 , Laura Jackisch 1 , Jinus Samavat 1 , Philip G McTernan 2 & Mark Christian 1

1University of Warwick, Coventry, UK; 2Nottingham Trent University, Nottingham, UK

Background: The acquisition of brown-adipocyte-properties by white-adipocytes (BRITE-adipocytes) is an appealing-prospect to combat obesity and type-2-diabetes-Mellitus (T2DM). This may support counteracting the impact of inflammation and mitochondrial-dysfunction, which contribute to the obesity-pathogenesis. However, our previous-finding shave shown that the gut-derived-inflammatory-agent endotoxin can increase the inflammatory-response in white-adipose-tissue impacted by obesity and T2DM, although its effect on the browning-process is unknown. Therefore, the objective of this study was to (1) investigate the in-vitro-effect of endotoxin on the browning-process in human-adipocytes; (2) define the expression of brown-fat-genes and inflammatory-genes in human-abdominal-subcutaneous (AbdSc) and omental (AbdOm) adipose-tissue-cohort (AT; n=128 female; age: 31.6±0.63) to determine the influence of adiposity, AT-depot, inflammation and mitochondrial-function.

Methods: Human-primary-adipocytes were differentiated with or without Rosiglitazone, which promotes adipocytes-browning, with or without endotoxin (100 ng/ml). Differentiated-cells were treated with isoproterenol to induce UCP1. AbdSc and AbdOm AT-biopsies were collected with ethical-approval during elective-surgeries. RNA from both cultured-adipocytes and AT was extracted and gene-expression was quantified by qRT-PCR.

Results: Endotoxin significantly reduced the BRITE-phenotype in the Rosiglitazone-treated-cells by reducing the key-brown-fat-genes-expression UCP1 (P<0.05), CIDEA (P<0.05), ELOVL3 (P<0.05), PLIN5 (P<0.05), SLC27A2 (P<0.05). Furthermore, endotoxin reduced key-mitochondrial-gene-expression (FIS1, DRP1, OPA1, MFN2, P<0.05). In addition, adiposity was associated with significantly reduced-expression of the key-brown-fat-genes (≈40%, P<0.05) and there was strong negative-correlation between BMI and brown-fat-genes in AbdSc-AT and AbdOm-AT (P<0.05). As anticipated adiposity significantly-increased inflammatory-genes-expression: IL6, MCP1, TNFα, IL1ß (≈30%, P<0.05) in both AbdOm-AT and AbdSc-AT. Interestingly, there were negative-correlations between inflammatory-genes and brown-fat-genes in AbdOm-AT (P<0.05), and direct positive-correlation between mitochondrial and brown-fat-genes in AT (P<0.05).

Conclusions: Endotoxin appears to reduce the in-vitro BRITE-phenotype-capacity in adipocytes due to enhanced-mitochondrial-dysfunction and inflammation, which is exacerbated with increasing adiposity. Taken together, subjects with obesity and T2DM would appear to have a reduced-capability to promote a BRITE-phenotype in WAT, as a means to reduce further weight-gain than lean non-diabetic-individuals.

Volume 65

Society for Endocrinology BES 2019

Brighton, United Kingdom
11 Nov 2019 - 13 Nov 2019

Society for Endocrinology 

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