The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment

Ranganathan, Gouri; Ünal, Reşat; Pokrovskaya, Irina D.; Yao-Borengasser, Aiwei; Phanavanh, Bounleut; Lecka‐Czernik, Beata; Rasouli, Neda; Kern, Philip A.

doi:10.1194/jlr.m600248-jlr200

Cited by 157 publications

(126 citation statements)

References 43 publications

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“…In agreement with our findings, DGAT and FASN mRNA expression in adipose tissue have been shown to correlate strongly and positively with IS, which was increased further following treatment with the peroxisome proliferatoractivated receptor gamma agonist pioglitazone [37]. In addition, fat cell lipogenesis in vitro was shown to correlate strongly and positively with IS, both basally and after insulin stimulation [38].…”

Section: Discussionsupporting

confidence: 91%

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

et al. 2009

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Aims/hypothesis Previous studies have shown relationships between fatty acid ratios in adipose tissue triacylglycerol (TG), adipocyte size and measures of insulin sensitivity. We hypothesised that variations in adipose tissue de novo lipogenesis (DNL) in relation to adiposity might explain some of these observations. Methods In a cross-sectional study, subcutaneous abdominal adipose tissue biopsies from 59 people were examined in relation to fasting and post-glucose insulin sensitivity. Adipocyte size, TG fatty acid composition and mRNA expression of lipogenic genes were determined. Results We found strong positive relationships between adipose tissue TG content of the fatty acids myristic acid (14:0) and stearic acid (18:0) with insulin sensitivity (HOMA model) (p<0.01 for each), and inverse relationships with adipocyte size (p<0.01, p<0.05, respectively).

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Section: Discussionsupporting

confidence: 91%

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

et al. 2009

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“…Overexpression of DGAT correlates with increased TAG storage in adipose tissue, skeletal muscle and liver (62)(63)(64) . DGAT1 expression in adipocytes and adipose tissue is up-regulated by PPARg (65)(66)(67) . HFDfed Ap2-Dgat1 mice overexpressing DGAT1 in both macrophages and adipocytes became obese; however, they were protected from the associated metabolic and inflammatory perturbations.…”

Section: Fatty Acids and Adipose Tissue Macrophage Polarisationmentioning

confidence: 99%

Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue

et al. 2011

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High-fat diet-induced obesity is associated with a chronic state of low-grade inflammation, which pre-disposes to insulin resistance (IR), which can subsequently lead to type 2 diabetes mellitus. Macrophages represent a heterogeneous population of cells that are instrumental in initiating the innate immune response. Recent studies have shown that macrophages are key mediators of obesity-induced IR, with a progressive infiltration of macrophages into obese adipose tissue. These adipose tissue macrophages are referred to as classically activated (M1) macrophages. They release cytokines such as IL-1β, IL-6 and TNFα creating a pro-inflammatory environment that blocks adipocyte insulin action, contributing to the development of IR and type 2 diabetes mellitus. In lean individuals macrophages are in an alternatively activated (M2) state. M2 macrophages are involved in wound healing and immunoregulation. Wound-healing macrophages play a major role in tissue repair and homoeostasis, while immunoregulatory macrophages produce IL-10, an anti-inflammatory cytokine, which may protect against inflammation. The functional role of T-cell accumulation has recently been characterised in adipose tissue. Cytotoxic T-cells are effector T-cells and have been implicated in macrophage differentiation, activation and migration. Infiltration of cytotoxic T-cells into obese adipose tissue is thought to precede macrophage accumulation. T-cell-derived cytokines such as interferon γ promote the recruitment and activation of M1 macrophages augmenting adipose tissue inflammation and IR. Manipulating adipose tissue macrophages/T-cell activity and accumulation in vivo through dietary fat modification may attenuate adipose tissue inflammation, representing a therapeutic target for ameliorating obesity-induced IR.

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“…2 Like excessive adiposity, impaired adipogenesis is associated with insulin resistance, 3 and insufficient adipose tissue causes glucose intolerance, which could be reversed by the presence of adipose tissue. [4][5][6] On the other hand, adequate lipid storage in the adipose tissue, 7 or induction of adipogenesis improves insulin sensitivity. [8][9][10] Therefore, understanding the regulation of adipocyte differentiation by cellular and extracellular factors is crucial for better management of chronic conditions such as obesity, insulin resistance and lipodystrophy.…”

Section: Introductionmentioning

confidence: 99%

Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene

et al. 2007

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Objective: Understanding the regulation of adipocyte differentiation by cellular and extracellular factors is crucial for better management of chronic conditions such as obesity, insulin resistance and lipodystrophy. Experimental infection of rats with a human adenovirus type 36 (Ad-36) improves insulin sensitivity and promotes adipogenesis, reminiscent of the effect of thiozolinediones. Therefore, we investigated the role of Ad-36 as a novel regulator of the adipogenic process. Design and Results: Even in the absence of adipogenic inducers, infection of 3T3-L1 preadipocytes and human adipose-derived stem cells (hASC) by Ad-36, but not Ad-2 that is another human adenovirus, modulated regulatory points that spanned the entire adipogenic cascade ranging from the upregulation of cAMP, phosphatidylinositol 3-kinase and p38 signaling pathways, downregulation of Wnt10b expression, and increased expression of CCAAT/enhancer binding protein-b and peroxisome proliferator-activated receptor g2 and consequential lipid accumulation. Next, we identified that E4 open reading frame (orf)-1 gene of the virus is necessary and sufficient for Ad-36-induced adipogenesis. Selective knockdown of E4 orf-1 by RNAi abrogated Ad-36-induced adipogenic signaling cascade in 3T3-L1 cells and hASC. Compared to the null vector, selective expression of Ad-36 E4 orf-1 in 3T3-L1 induced adipogenesis, which was abrogated when the PDZ-binding domain of the protein was deleted. Conclusion: Thus, Ad-36 E4 orf-1 is a novel inducer of rodent and human adipocyte differentiation process.

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The lipogenic enzymes DGAT1, FAS, and LPL in adipose tissue: effects of obesity, insulin resistance, and TZD treatment

Cited by 157 publications

References 43 publications

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

Markers of de novo lipogenesis in adipose tissue: associations with small adipocytes and insulin sensitivity in humans

Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue

Human adenovirus Ad-36 induces adipogenesis via its E4 orf-1 gene

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