Mediators of Impaired Adipogenesis in Obesity-Associated Insulin Resistance and T2DM

Al-Sulaiti, Haya; Dömling, Alexander; Elrayess, Mohamed A.

doi:10.5772/intechopen.88746

Cited by 10 publications

(6 citation statements)

References 189 publications

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“…Modulators, including GATA3, were shown to be highly expressed in insulin-resistant tissues and to be responsible for preventing adipogenesis. Despite its potential role in obesity prevention, such approach has a great risk of preventing adipogenesis, which is required to maintain adipose tissue homeostasis and insulin sensitivity [ 29 ]. GATA3-associated impaired adipogenesis affects lipid homeostasis contributing to body fat distribution, causing the deposition of ectopic fat in the liver, kidney, and skeletal muscles; triggering insulin resistance; and increasing the risk of T2D [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity

Al-Jaber

Mohamed²,

Govindharajan³

et al. 2022

IJMS

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Impaired adipogenesis is associated with the development of insulin resistance and an increased risk of type 2 diabetes (T2D). GATA Binding Protein 3 (GATA3) is implicated in impaired adipogenesis and the onset of insulin resistance. Therefore, we hypothesize that inhibition of GATA3 could promote adipogenesis, restore healthy fat distribution, and enhance insulin signaling. Primary human preadipocytes were treated with GATA3 inhibitor (DNAzyme hgd40). Cell proliferation, adipogenic capacity, gene expression, and insulin signaling were measured following well-established protocols. BALB/c mice were treated with DNAzyme hgd40 over a period of 2 weeks. Liposomes loaded with DNAzyme hgd40, pioglitazone (positive), or vehicle (negative) controls were administered subcutaneously every 2 days at the right thigh. At the end of the study, adipose tissues were collected and weighed from the site of injection, the opposite side, and the omental depot. Antioxidant enzyme (superoxide dismutase and catalase) activities were assessed in animals’ sera, and gene expression was measured using well-established protocols. In vitro GATA3 inhibition induced the adipogenesis of primary human preadipocytes and enhanced insulin signaling through the reduced expression of p70S6K. In vivo GATA3 inhibition promoted adipogenesis at the site of injection and reduced MCP-1 expression. GATA3 inhibition also reduced omental tissue size and PPARγ expression. These findings suggest that modulating GATA3 expression offers a potential therapeutic benefit by correcting impaired adipogenesis, promoting healthy fat distribution, improving insulin sensitivity, and potentially lowering the risk of T2D.

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Section: Discussionmentioning

confidence: 99%

In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity

Al-Jaber

Mohamed²,

Govindharajan³

et al. 2022

IJMS

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“…Our novel data indicate significant elevation in various serum triglycerides, particularly the polyunsaturated triglycerides C20:4_C34:3 and C18:2_C38:6, in the PCOS pregnant women. Although, triacylglycerols are not metabolically active, their breakdown products, including fatty acids and diacylglycerols, play important roles in cell signaling ( 8 , 20 ). Indeed, our subsequent enrichment analysis showed significant elevations in triglycerides containing essential polyunsaturated fatty acid (PUFA) with critical cell signaling properties, namely C20:4 (arachidonic acid), C18:0 (linoleic acid) and C16:0 (palmitic acid) in the PCOS group.…”

Section: Discussionmentioning

confidence: 99%

Metabolomic Profiling of Pregnancies With Polycystic Ovary Syndrome Identifies a Unique Metabolic Signature and Potential Predictive Biomarkers of Low Birth Weight

et al. 2021

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BackgroundPolycystic ovary syndrome (PCOS) is a complex syndrome with clinical features of an endocrine/metabolic disorder. Various metabolites show significant association with PCOS; however, studies comparing the metabolic profile of pregnant women with and without PCOS are lacking. In this study, metabolomics analysis of blood samples collected from PCOS women and age and BMI matched controls in the second trimester of pregnancy was performed to identify metabolic differences between the two groups and determine their association with pregnancy outcome.MethodsSixteen PCOS and fifty-two healthy women in their second trimester underwent targeted metabolomics of plasma samples using tandem mass spectrometry with the Biocrates MxP® Quant 500 Kit. Linear regression models were used to identify the metabolic alterations associated with PCOS, followed by enrichment and Receiver Operating Characteristic (ROC) analyses to determine the best indicators of pregnancy outcomes.ResultsPCOS women had lower birth weight babies compared to healthy controls. As a group, systolic blood pressure (SBP) at both second trimester and at delivery negatively correlated with birth weight. Regression models indicated significant increases in the triglycerides C20:4_C34:3 and C18:2_C38:6 in the PCOS group [false discovery rate (FDR) <0.05]. Enrichment analysis revealed significant elevations in triglycerides containing arachidonic acid, linoleic acid and palmitic acid in the PCOS group. A number of indicators of baby birth weight were identified including SBP at delivery, hexosylceramide (d18:2/24:0), ceramide (d18.0/24.1) and serine, with an AUC for all predictors combined for low birth weight (≤2500grams) of 0.88 (95%CI: 0.75-1.005, p<0.001).ConclusionsPCOS pregnancies resulted in babies with a lower birth weight, marked by a unique metabolic signature that was enriched with specific triglycerides and unsaturated fatty acids. The functional significance of these associations needs further investigation.

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“…The adipose tissue is a dynamic part of the endocrine system that plays a crucial role in maintaining energy balance and nutritional homeostasis [37]. Mature adipocytes constitute the most abundant distinctive cell type in the adipose tissue, occupying 90% of its volume [38].…”

Section: The Role Of Adipogenesis In Obesity-associated Ir and T2dmmentioning

confidence: 99%

“…Various studies have reported the beneficial effects of PUFAs on lipid-related human disorders [127][128][129][130][131], which largely depend on the structure of the fatty acids and their metabolic properties. PUFAs can inhibit lipogenic gene transcription by downregulating the expression SREBPs [132][133][134][135] and act as antagonists of liver X receptors (LXR) [136,137] and as agonists for PPARs [122-124, 138, 139]. PUFAs, but not saturated or MUFAs, inhibit lipogenic genes by downregulating SREBP-1c.…”

Section: Fatty Acid Signalingmentioning

confidence: 99%

Adipose Tissue - An Update

Szablewski¹

2019

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Obesity has become a global health issue due to its high prevalence and associated comorbidities including insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Obesity is associated with the expansion of adipose tissues through hypertrophy of mature adipocytes and differentiation of local preadipocytes in a process known as adipogenesis to store excess triacylglycerols (TAGs). Impairment of adipogenesis leads to ectopic fat deposition in skeletal muscles, liver, and kidneys, triggering IR in these tissues and increased risk of T2DM. Many factors contribute to impaired adipogenesis including obesity-associated mild chronic inflammation, oxidative stress, and fatty acid signaling. This review summarizes recent literature covering mediators of impaired adipogenesis and underlying molecular pathways.

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Mediators of Impaired Adipogenesis in Obesity-Associated Insulin Resistance and T2DM

Cited by 10 publications

References 189 publications

In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity

In Vitro and In Vivo Validation of GATA-3 Suppression for Induction of Adipogenesis and Improving Insulin Sensitivity

Metabolomic Profiling of Pregnancies With Polycystic Ovary Syndrome Identifies a Unique Metabolic Signature and Potential Predictive Biomarkers of Low Birth Weight

Adipose Tissue - An Update

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