1,2-Diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo.

Turinsky, J.; O’Sullivan, David; Bayly, B. P.

doi:10.1016/s0021-9258(17)44844-7

Cited by 235 publications

(41 citation statements)

References 40 publications

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“…Our results and previously published data (Jornayvaz et al, ; Samuel et al, ; Turinsky et al, ) indicate that intracellular lipids accumulation affects insulin‐signaling pathway. Numerous studies reported that the accumulation of DAG negatively affects the insulin pathway in liver on IRS level (Galbo et al, ; Samuel et al, , ; Samuel & Shulman, ; Shulman, ; Turinsky et al, ). The phosphorylation of IRS on Ser/Thr residue results in inhibitory signal on insulin‐signaling pathway, whereas the phosphorylation on Tyr residue causes activation of this cascade.…”

Section: Discussionsupporting

confidence: 84%

“…U. Blachnio-Zabielska, Chacinska, Vendelbo, & Zabielski, 2016;Oakes et al, 1994;Schmitz-Peiffer, 2000;Schmitz-Peiffer, Craig, & Biden, 1999;Straczkowski et al, 2007Straczkowski et al, , 2004Zabielski et al, 2017). However, in 1990, Turinsky has noticed an increased content of DAG and Cer in liver of obese, insulin-resistant Zucker rats (Turinsky, O'Sullivan, & Bayly, 1990). Then, the association of IRes with hepatic DAG accumulation was proven several times by other research (Kumashiro et al, 2011;Magkos et al, 2012;Perry, Samuel, Petersen, & Shulman, 2014).…”

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confidence: 97%

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The effect of high‐fat diet and inhibition of ceramide production on insulin action in liver

Zabielski

Daniluk

Hady

et al. 2018

Journal Cellular Physiology

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Liver, as one of the most important organs involved in lipids and glucose metabolism, is perceived as a key tissue for pharmacotherapy of insulin resistance (IRes) and type 2 diabetes. Ceramides (Cer) are biologically active lipids, which accumulation is associated with the induction of muscle IRes. We sought to determine the role of intrahepatic bioactive lipids production on insulin action in liver of insulin-resistant rats and after myriocin administration. The experiments were conducted on male Wistar rats divided into three groups: Control, fed high-fat diet (HFD), and fed HFD and treated with myriocin (HFD/Myr). Before sacrifice, the animals were infused with a [U- C]palmitate to calculate lipid synthesis rate by means of tracer incorporation technique in particular lipid groups. Liver Cer, diacylglycerols (DAG), acyl-carnitine concentration, and isotopic enrichment were analyzed by LC/MS/MS. Proteins involved in lipid metabolism and insulin pathway were analyzed by western blot analysis. An OGTT and ITT was also performed. HFD-induced IRes and increased both the synthesis rate and the content of DAG and Cer, which was accompanied by inhibition of an insulin pathway. Interestingly, myriocin treatment reduced synthesis rate not only of Cer but also DAG and improved insulin sensitivity. We conclude that the insulin-sensitizing action of myriocin in the liver is a result of the lack of inhibitory effect of lipids on the insulin pathway, due to the reduction of their synthesis rate. This is the first study showing how the synthesis rate of individual lipid groups in liver changes after myriocin administration.

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Section: Discussionsupporting

confidence: 84%

mentioning

confidence: 97%

The effect of high‐fat diet and inhibition of ceramide production on insulin action in liver

Zabielski

Daniluk

Hady

et al. 2018

Journal Cellular Physiology

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“…DGs are the building blocks for glycerol(phospho)lipids, and triglycerides are one of the precursors (15). DG concentration has been shown to be increased with obesity in both animal models and clinical studies (23,55,62,63). PE is considered an ether-linked phospholipid and known to have antioxidant properties (12,16,60).…”

Section: Discussionmentioning

confidence: 99%

Obesity leads to distinct metabolomic signatures in follicular fluid of women undergoing in vitro fertilization

Ruebel

Piccolo

Mercer

et al. 2019

American Journal of Physiology-Endocrinology and Metabolism

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Although obesity negatively influences the metabolic homeostasis of cells within a broad range of tissues, its impact on oocyte metabolism is not fully understood. Prior evidence suggests that obesity increases expression of oocyte genes associated with inflammation, oxidative stress, and lipid metabolism; however, the metabolic impact of these genetic differences is not known. To address this gap, we conducted an exploratory assessment of the follicular fluid (FF) metabolome in eight overweight/obese (OW) and nine normal-weight (NW) women undergoing in vitro fertilization. FF and serum were collected and analyzed by untargeted metabolomics using gas chromatography-quadrupole time-of-flight mass spectrometry and charged-surface hybrid column-electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Untargeted metabolomics identified obesity-associated changes in FF metabolites related to oxidative stress/antioxidant capacity, xenometabolism/amino acid biosynthesis, and lipid metabolism. Discriminant FF metabolites included elevated uric acid, isothreonic acid, one unknown primary metabolite, and six unknown complex lipids in OW compared with NW women. Conversely, 2-ketoglucose dimethylacetal, aminomalonate, two unknown primary metabolites, and two unknown complex lipids were decreased in FF of OW relative to NW women. Indole-3-propionic acid (IPA), a bacteria-derived metabolite, was also decreased in both FF and serum of OW women ( P < 0.05). The significant correlation between antioxidant IPA in serum and FF ( R = 0.95, P < 0.0001) suggests a potential serum biomarker of FF antioxidant status or reflection of the gut metabolism interaction with the follicle. These results suggest that obesity has important consequences for the follicular environment during the preconception period, a window of time that may be important for lifestyle interventions to ameliorate obesity-associated risk factors.

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“…On the other hand, hydrolysis of phosphatidylinositol-4,5-bisphosphate occurs as a result of the action of phospholipase C-β. Intramuscular accumulation of DAG was found in insulin-resistant rats fed high-fat diet [57] as well as Zucker rats [58]. Moreover, a threefold increase in liver DAG content was observed in rats infused with intralipid, resulting in inhibition of the insulin pathway.…”

Section: Diacylglycerols (Dag)mentioning

confidence: 95%

Obesity, Bioactive Lipids, and Adipose Tissue Inflammation in Insulin Resistance

2020

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Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes. The exact mechanism by which adipose tissue induces insulin resistance is still unclear. It has been demonstrated that obesity is associated with the adipocyte dysfunction, macrophage infiltration, and low-grade inflammation, which probably contributes to the induction of insulin resistance. Adipose tissue synthesizes and secretes numerous bioactive molecules, namely adipokines and cytokines, which affect the metabolism of both lipids and glucose. Disorders in the synthesis of adipokines and cytokines that occur in obesity lead to changes in lipid and carbohydrates metabolism and, as a consequence, may lead to insulin resistance and type 2 diabetes. Obesity is also associated with the accumulation of lipids. A special group of lipids that are able to regulate the activity of intracellular enzymes are biologically active lipids: long-chain acyl-CoAs, ceramides, and diacylglycerols. According to the latest data, the accumulation of these lipids in adipocytes is probably related to the development of insulin resistance. Recent studies indicate that the accumulation of biologically active lipids in adipose tissue may regulate the synthesis/secretion of adipokines and proinflammatory cytokines. Although studies have revealed that inflammation caused by excessive fat accumulation and abnormalities in lipid metabolism can contribute to the development of obesity-related insulin resistance, further research is needed to determine the exact mechanism by which obesity-related insulin resistance is induced.

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1,2-Diacylglycerol and ceramide levels in insulin-resistant tissues of the rat in vivo.

Cited by 235 publications

References 40 publications

The effect of high‐fat diet and inhibition of ceramide production on insulin action in liver

The effect of high‐fat diet and inhibition of ceramide production on insulin action in liver

Obesity leads to distinct metabolomic signatures in follicular fluid of women undergoing in vitro fertilization

Obesity, Bioactive Lipids, and Adipose Tissue Inflammation in Insulin Resistance

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