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REGULATION OF TRIGGER RECEPTOR EXPRESSED ON MYELOID CELLS-1 (TREM-1) IN HEPATOCYTES (IN-VIVO) AND HEPG2 CELL LINE (IN-VITRO) DURING INSULIN RESISTANCE Kalyana Nandipati, Poona Sharma, Saravanan Subramnian*, Devendra K. Agrawal Surgery, Creighton , Omaha, NE
Triggering Receptor Expressed on Myeloid cells-1 (TREM-1) has been recently recognized as a potent amplifier of pro-inflammatory innate immune response. However, the significant role of TREM-1 remains unclear in non-infectious diseases such as obesity, insulin resistance etc. We examined the expression of TREM-1 and TREM-2 in hepatocytes using dual-immunofluorescence staining in liver biopsy samples from human study populations [non-obese (NO; N=6), obese non-diabteics (OND; N=11) and obese diabetics (OD; N=11)] and Yucatan micro-swine model [normal diet (ND; N=3) and high fructose and high cholesterol diet (HFHCD; N=7)]. We also examined the mRNA and protein expression of TREM-1 and TREM-2 in in-vitro HepG2 cell line with or without stimulation of palmitic acid (PA: 100, 250, 500, 750 and 1000µM) and glucose (GL: 5, 10, 15, 20, 25mM). The dual immunofluorescence study revealed that the mean fluorescence identity (MFI) of TREM-1 was significantly up-regulated and co-localized with albumin hepatocyte marker in OD patients compared to OND (16.61±5.45 vs 4.44±2.37; p<0.0001) and NO (16.61±5.45 vs 2.26±0.32; p<0.0001) groups; however, the levels of TREM-2 co-localized with albumin hepatocyte marker were significantly (p<0.05) down regulated. The OD population had shown increased TREM-1 expression [11/11 (100%) vs 5/11 (45.4%); p<0.0001) in hepatocytes compared to OND. The expression of TREM-1 in hepatocytes was highly correlated with FFA levels and HOMA-IR in OD patients. In in-vivo model, increased expression of TREM-1 (MFI: 6.96±3.77 vs 1.17±0.52; p<0.05) co-localized with albumin marker in HFHCD group compared to ND group was observed. We also found significantly increased mRNA [PA: (4.57±0.42 vs 1.05±0.04; p<0.001); GLU: (3.98±0.13 vs 1.06±0.09; p<0.0001)], protein [PA: (3.70±0.14 vs 1.12±0.17; p<0.0001); GLU: (3.89±0.09 vs 1.06±0.080; p<0.0001] and soluble TREM-1 expression [PA: Elisa (15.09±1.48 vs 82.93±1.68 pg/ml; p<0.0001); GLU: Elisa (15.79±0.41 vs 63.19±2.86 pg/ml; p<0.0001)] in HepG2 cell line with palmitic acid (1000µM) or glucose (25mM) stimulation compared to non-stimulated cells. Thus TREM-1 in hepatocytes may play a significant role in the pathophysiology of obesity and associated co-morbidities. Hence, TREM-1 may serve as a prognostic marker for insulin resistance. Back to 2017 Posters |
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