LIPC variants as genetic determinants of adiposity status, visceral adiposity indicators, and triglyceride-glucose (TyG) index-related parameters mediated by serum triglyceride levels

Teng, Michelle H.; Wu, Semon; Er, Leay Kiaw; Hsu, Lung‐An; Chou, Hsin Hua; Ko, Yu‐Lin

doi:10.1186/s13098-018-0383-9

Cited by 14 publications

(5 citation statements)

References 63 publications

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“…VAI and LAP combine both anthropometric and metabolic variables to evaluate, respectively, adiposity dysfunction and lipid overaccumulation, whereas TyG includes only metabolic variables. TyG is among the most mentioned insulin resistance indices in the literature [29][30][31][32][33][34][35][36]. TyG has also been suggested as a promising biomarker for glycaemic control in people with type 2 diabetes [30], even better than HOMA [29].…”

Section: Discussionmentioning

confidence: 99%

Novel metabolic indices and incident type 2 diabetes among women and men: the Rotterdam Study

et al. 2019

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Aims/hypothesis Both visceral and truncal fat have been associated with metabolic disturbances. We aimed to investigate the associations of several novel metabolic indices, combining anthropometric and lipid measures, and dual-energy x-ray absorptiometry (DXA) measurements of body fat, with incident type 2 diabetes among women and men from the large population-based Rotterdam Study. Methods Cox proportional hazards models were used to investigate associations of visceral adiposity index (VAI), lipid accumulation product (LAP), the product of triacylglycerol and glucose (TyG), their formula components and DXA measures with incident type 2 diabetes. Associations were adjusted for traditional diabetes risk factors. Results Among 5576 women and 3988 men free of diabetes, 511 women and 388 men developed type 2 diabetes during a median follow-up of 6.5 years. In adjusted models, the three metabolic indices VAI (per 1 SD naturally log-transformed HR; 95%

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Section: Discussionmentioning

confidence: 99%

Novel metabolic indices and incident type 2 diabetes among women and men: the Rotterdam Study

et al. 2019

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“…Through the analysis of the TUSC3 microarray, LIPC was the most related gene to TUSC3. Synthesized in the endoplasmic reticulum of liver parenchymal cells, LIPC containing N-linked high mannose type was transferred to Golgi and secreted as an active form [24]. Based on previous studies, LIPC plays a disparate function in different cancers [12][13][14][15][16].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of TUSC3 promotes EMT and hepatocellular carcinoma progression through LIPC/AKT axis

Deng

Chen

et al. 2022

J Transl Med

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Background Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors in the digestive tract. Tumor Suppressor Candidate 3 (TUSC3) is one subunit of the endoplasmic reticulum Oligosaccharyl transferase (OST) complex, which plays an important role in N-glycosylation during the protein folding process. However, the role of TUSC3 in the initiation and progression of HCC has not been mentioned yet. In the present study, we aim to investigate the effects of TUSC3 on the initiation and progression of HCC. Methods Immunohistochemical assay and qRT-PCR were used to detect the expression of TUSC3 and lipase C hepatic type (LIPC) in HCC tissue and cells. Loss-of-function and gain-of-function were applied to detect the function of TUSC3 and LIPC in vivo and in vitro. Immunofluorescence assay and co-immunoprecipitation were used to detect the relationship between TUSC3 and LPC. Western blot was applied to detect the expression of epithelial–mesenchymal transition (EMT) markers and the Akt signaling pathway. Results TUSC3 was aberrantly decreased in hepatocellular carcinoma tissues compared to the matched adjacent normal tissues, which resulted in bigger size of tumor (P = 0.001, Table 2), worse differentiation (P = 0.006, Table 2) and an advanced BCLC stage. Down-regulation of TUSC3 led to the enhanced proliferation and migration of hepatocellular carcinoma cells in vivo and vitro, whereas the opposite effect could be observed in the TUSC3-overexpression group. The analysis of TUSC3 microarray showed that LIPC, a glycoprotein primarily synthesized and secreted by hepatocytes, was a downstream target of TUSC3, and it negatively modulated the development of HCC. The morphological changes in HCC cells indicated that TUSC3 regulated the epithelial-mesenchymal transition (EMT). Mechanistically, TUSC3 inhibited EMT progression through the LIPC/AKT axis. Conclusion Down-regulation of TUSC3 promotes EMT progression by activating AKT signaling via targeting LIPC in HCC, which is probably the possible mechanism driving TUSC3-deficient hepatocellular carcinoma cells toward a malignant phenotype.

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“…There are studies based on Indian population also (24) that have explored the effect of genetics on obesity, and related traits, however, VAI, and BAI remain unexplored. There are only 2 variants, rs2043085, and rs1532085 at LIPC that have been identi ed in Taiwanese population for VAI (25), and none for BAI. Understanding the genetic underpinnings of the indices is relevant as it will be critical in understanding the complex interplay between individual anthropometric measures, and biochemical parameters.…”

Section: Introductionmentioning

confidence: 99%

Novel genomic variants related to Visceral Adiposity Index (VAI) and Body Adiposity Index (BAI) in Indian Sib-pairs

Walia,

Agarwal,

Lyngdoh

et al. 2023

Preprint

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Background: Obesity is among the leading public health threats globally. Over the last few years, Visceral Adiposity Index (VAI), and Body Adiposity Index (BAI), derived from anthropometric, and biochemical measures, have gained importance as a measure of obesity. However, unlike other common indices like body mass index, and waist circumference, the genetic predisposition of VAI, and BAI under-examined. Methods: 2265 sib-pairs from Indian Migration Study were used for examining the association of genetic variants from the Cardio-Metabochip array with VAI, and BAI. Mixed linear regression models were run, and all inferences were based on the within-sib component of the Fulker’s association models. Gene-environment/lifestyle interaction analyses were also undertaken. Results: rs6659428 at LOC400796|SEC16B (ꞵ=0.26, SE =0.05), and rs7611535 at DRD3|LOC645180 (ꞵ=0.18,SE =0.04) were associated with VAI at suggestive significance value of <8.21×10-6. For BAI, rs73300702 at JAZF1-AS1 (ꞵ=0.27,SE=0.06), was the top hit at p-value<8.21×10-6. rs6659428 showed marginal effect modification with location (ꞵ=0.26,SE=0.13,p-value=0.047), and rs73300702 with physical activity (ꞵ=-0.29,SE=0.14,p-value=0.034). Conclusion: We report three novel genetic loci associated with VAI, and BAI in Indians. These findings need to be confirmed with longitudinal or validation studies in other populations and related functional studies for understanding the biological mechanisms of obesity and related-cardiometabolic conditions.

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LIPC variants as genetic determinants of adiposity status, visceral adiposity indicators, and triglyceride-glucose (TyG) index-related parameters mediated by serum triglyceride levels

Cited by 14 publications

References 63 publications

Novel metabolic indices and incident type 2 diabetes among women and men: the Rotterdam Study

Novel metabolic indices and incident type 2 diabetes among women and men: the Rotterdam Study

Downregulation of TUSC3 promotes EMT and hepatocellular carcinoma progression through LIPC/AKT axis

Novel genomic variants related to Visceral Adiposity Index (VAI) and Body Adiposity Index (BAI) in Indian Sib-pairs

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