scholarly journals Adipose tissue and the insulin resistance syndrome

2001 ◽  
Vol 60 (3) ◽  
pp. 375-380 ◽  
Author(s):  
Keith N. Frayn
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Insulin Resistance Syndrome ◽  
Fat Storage ◽  
Postprandial Period ◽  
Fat Mobilization ◽  
Lipid Metabolites

Obesity is associated with insulin resistance. Insulin resistance underlies a constellation of adverse metabolic and physiological changes (the insulin resistance syndrome) which is a strong risk factor for development of type 2 diabetes and CHD. The present article discusses how accumulation of triacylglycerol in adipocytes can lead to deterioration of the responsiveness of glucose metabolism in other tissues. Lipodystrophy, lack of adipose tissue, is also associated with insulin resistance. Any plausible explanation for the link between excess adipose tissue and insulin resistance needs to be able to account for this observation. Adipose tissue in obesity becomes refractory to suppression of fat mobilization by insulin, and also to the normal acute stimulatory effect of insulin on activation of lipoprotein lipase (involved in fat storage). The net effect is as though adipocytes are ‘full up’ and resisting further fat storage. Thus, in the postprandial period especially, there is an excess flux of circulating lipid metabolites that would normally have been ‘absorbed’ by adipose tissue. This situation leads to fat deposition in other tissues. Accumulation of triacylglycerol in skeletal muscles and in liver is associated with insulin resistance. In lipodystrophy there is insufficient adipose tissue to absorb the postprandial influx of fatty acids, so these fatty acids will again be directed to other tissues. This view of the link between adipose tissue and insulin resistance emphasises the important role of adipose tissue in ‘buffering’ the daily influx of dietary fat entering the circulation and preventing excessive exposure of other tissues to this influx.

scholarly journals Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

2013 ◽  
Vol 15 (1) ◽  
Author(s):  
Charmaine S. Tam ◽  
Leanne M. Redman
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Proinflammatory Mediators ◽  
Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

scholarly journals Collagen 24 α1 Is Increased in Insulin-Resistant Skeletal Muscle and Adipose Tissue

2020 ◽  
Vol 21 (16) ◽  
pp. 5738
Author(s):  
Xiong Weng ◽  
De Lin ◽  
Jeffrey T. J. Huang ◽  
Roland H. Stimson ◽  
David H. Wasserman ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Resistant ◽  
Global View ◽  
Novel Association ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

Aberrant extracellular matrix (ECM) remodelling in muscle, liver and adipose tissue is a key characteristic of obesity and insulin resistance. Despite its emerging importance, the effective ECM targets remain largely undefined due to limitations of current approaches. Here, we developed a novel ECM-specific mass spectrometry-based proteomics technique to characterise the global view of the ECM changes in the skeletal muscle and liver of mice after high fat (HF) diet feeding. We identified distinct signatures of HF-induced protein changes between skeletal muscle and liver where the ECM remodelling was more prominent in the muscle than liver. In particular, most muscle collagen isoforms were increased by HF diet feeding whereas the liver collagens were differentially but moderately affected highlighting a different role of the ECM remodelling in different tissues of obesity. Moreover, we identified a novel association between collagen 24α1 and insulin resistance in the skeletal muscle. Using quantitative gene expression analysis, we extended this association to the white adipose tissue. Importantly, collagen 24α1 mRNA was increased in the visceral adipose tissue, but not the subcutaneous adipose tissue of obese diabetic subjects compared to lean controls, implying a potential pathogenic role of collagen 24α1 in obesity and type 2 diabetes.

scholarly journals The role of nonesterified fatty acids in pathogenesis of cardiovascular diseases

2010 ◽  
Vol 16 (1) ◽  
pp. 93-103 ◽  
Author(s):  
M. V. Tsvetkova ◽  
V. N. Khirmanov ◽  
N. N. Zybina
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Risk Factor ◽  
Cardiovascular Diseases ◽  
Sudden Death

The paper reviews publications concerned the role of nonesterifi ed fatty acids (NEFA) in pathogenesis of cardiovascular diseases. NEFAs are four and more carbons chain length carbonic acids and they are presented in free form (nonesterifi ed) in human body. Plasma NEFAs are produced by the adipose tissue triglyceride lipolysis, another source are lipoproteins such as chylomicrons, very low density lipoproteins and intermediate density lipoproteins. Elevated NEFA concentrations in plasma are the risk factor of cardiovascular diseases and type 2 diabetes mellitus and the independent risk factor of hypertension and sudden death. NEFA plasma concentration is elevated in atherosclerosis, acute myocardial infarction, diabetes mellitus, obesity, hypertension, and often in metabolic syndrome. A probable cause of NEFAs accumulation in plasma may be overeating and low physical activity, which result in increase of adipose tissue mass, lipolysis intensifi cation and elevation of NEFAs concentration in plasma. The role of elevated plasma NEFA concentration in a number of conditions (abdominal obesity, atherogenic dyslipidemia, insulin resistance, type 2 diabetes mellitus, endothelial dysfunction, vascular infl ammation, atherosclerosis, hypertension, ischemic heart disease, rhythm disturbances, sudden death) and possible ways of their correction are discussed.

scholarly journals The role of the lipotoxicity in the pathogenesis of type 2 diabetes mellitus and obesity

2014 ◽  
Vol 11 (2) ◽  
pp. 8-12 ◽  
Author(s):  
F R Abdulkadirova ◽  
A S Ametov ◽  
E V Doskina ◽  
R A Pokrovskaya
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Type 2 Diabetes Mellitus ◽  
Diabetes Mellitus Type 2 ◽  
Comorbid Conditions ◽  
Fatty Acids Metabolism

Obesity is a major risk factor for diabetes mellitus type 2, cardiovascular diseases and associated comorbid conditions. It is traditionally considered that insulin resistance is dependent on glucose metabolism. However, in recent years more and more attention is devoted to the fatty acids metabolism, the increase in concentrations of which plays a significant role in the pathophysiological mechanisms associated with insulin resistance.

scholarly journals Abnormal Non Esterified Fatty Acid Suppression After a Mixed Meal Test in Patients With Partial Lipodystrophy

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A1-A2
Author(s):  
Maria Cristina Foss de Freitas ◽  
Baris Akinci ◽  
Elif A Oral
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Meal Test ◽  
Mixed Meal ◽  
Partial Lipodystrophy ◽  
Mixed Meal Test

Abstract Elevated levels of non-esterified fatty acids (NEFA) have been observed in individuals with several clinical scenarios of insulin resistance, such as in diabetes mellitus and lipodystrophy. Insulin is a well-known stimulator of de novo lipogenesis. Despite the reduction of adipose tissue mass, paradoxically elevated circulating NEFA concentrations have been observed in patients with different lipodystrophy syndromes. Aiming to understand the behavior of NEFA in lipodystrophy versus common Type 2 diabetes mellitus during feeding, we compared NEFA kinetics during a mixed meal test in patients with partial lipodystrophy (PL) and Type 2 diabetes mellitus (DM). We reviewed data from 17 PL patients (13F/4M, ages 12–64) matched by gender and BMI to 20 DM patients (13F/7M, ages 24–72). All patients were evaluated during fasting state and then underwent a mixed meal test (MMT). Blood samples were collected before (fasting) and at 30, 60, 90, 120, and 180 minutes post-meal to measure glucose, insulin, non-esterified free fatty acids (NEFA), and triglyceride levels. Adipose tissue insulin resistance (ADIPO-IR) and homeostatic model of insulin resistance (HOMA-IR) were calculated from the fasting measurements, and the area under the curve (AUC) and maximum percentage of change from baseline were calculated from the MMT data. Fasting insulin and triglyceride (Tg) levels were lower in the DM group compared to the PL group (Insulin: 24.4±13.7 vs. 68.0±67.2 pmol/L, p=0.003 and Tg: 168.0±107.7 vs. 1378.3±1927.3 mg/dL, p<0.001). HOMA-IR was significantly higher in the PL group compared to the DM group (6.0±2.1 vs. 3.3±1.5, p=0.005), as well as ADIPO-IR (297.0±241.1 vs. 115.3±80.1, p=0.03). NEFA, glucose and triglyceride AUC were significantly higher in the PL group compared to the DM group. Patients with PL had higher glucose and triglyceride levels throughout the MMT at all-time points. Interestingly, NEFA levels were similar in both groups at baseline, but the PL group suppressed NEFA less than DM group (54.9±13.3% vs. 69.2±11.1%, p=0.002) despite higher insulin levels. Additionally, we divided the PL group according to the presence of a pathogenic variant in the lamin A gene (n=8) versus those without mutations in this gene (n=9), but there were no notable differences among these subgroups with respect to NEFA levels at baseline or during the meal. These findings support the need to better understand and address the origins of abnormal NEFA kinetics and adipose tissue insulin resistance in PL patients.

scholarly journals Potential Roles of Adipocyte Extracellular Vesicle–Derived miRNAs in Obesity-Mediated Insulin Resistance

2020 ◽  
Author(s):  
Yujeong Kim ◽  
Ok-Kyung Kim
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Metabolic Disorders ◽  
Extracellular Vesicle ◽  
Extracellular Mirnas

ABSTRACT Recently, extracellular microRNAs (miRNAs) from adipose tissue have been shown to be involved in the development of insulin resistance. Here, we summarize several mechanisms explaining the pathogenesis of obesity-induced insulin resistance and associated changes in the expression of obesity-associated extracellular miRNAs. We discuss how miRNAs, particularly miR-27a, miR-34a, miR-141-3p, miR-155, miR210, and miR-222, in extracellular vesicles secreted from the adipose tissue can affect the insulin signaling pathway in metabolic tissue. Understanding the role of these miRNAs will further support the development of therapeutics for obesity and metabolic disorders such as type 2 diabetes.

scholarly journals Adipogenesis and lipotoxicity: role of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγcoactivator-1 (PGC1)

2007 ◽  
Vol 10 (10A) ◽  
pp. 1132-1137 ◽  
Author(s):  
Gema Medina-Gomez ◽  
Sarah Gray ◽  
Antonio Vidal-Puig
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Metabolic Complications ◽  
Peroxisome Proliferator Activated Receptor ◽  
Toxic Response ◽  
Increased Risk ◽  
And Function

AbstractObesity is characterised by an increase in the adipose deposits, resulting from an imbalance between food intake and energy expenditure. When expansion of the adipose tissue reaches its maximum limit, as in obesity, fat accumulates in non-adipose tissues such as liver, heart, muscle and pancreas, developing a toxic response known as lipotoxicity, a condition that promotes the development of insulin resistance and other metabolic complications. Thus, the lipotoxic state may contribute to the increased risk of insulin resistance, diabetes, fatty liver and cardiovascular complications associated with obesity.We are interested in studying adipose tissue, specifically how mechanisms of adipogenesis and remodelling of adipose tissue, in terms of size and function of the adipocytes, could be considered a strategy to increase the capacity for lipid storage and prevent lipotoxicity. The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors that regulate energy balance by promoting either energy deposition or energy dissipation. Under normal physiological conditions, PPARγ is mainly expressed in adipose tissue and regulates diverse functions such as the development of fat cells and their capacity to store lipids. The generation of PPARγ knockout mice, either tissue specific or isoform specific, has provided new models to study PPARγ’s role in adipose tissue differentiation and function and have highlighted the essential role of PPARγ in adipogenesis and lipogenesis.A second strategy to prevent lipotoxicity is to increase the capacity of tissues to oxidise fatty acids. PPARγcoactivator-1α is a coactivator of PPARγ that induces the expression of genes that promote the differentiation of preadipocytes to brown adipocytes. Recently, it has been implicated in increasing the oxidation of fatty acids via increasing mitochondrial capacity and function, making this co-factor a key candidate for the treatment of lipotoxicity.

scholarly journals Role of Muscle c-Jun NH2-Terminal Kinase 1 in Obesity-Induced Insulin Resistance

2009 ◽  
Vol 30 (1) ◽  
pp. 106-115 ◽  
Author(s):  
Guadalupe Sabio ◽  
Norman J. Kennedy ◽  
Julie Cavanagh-Kyros ◽  
Dae Young Jung ◽  
Hwi Jin Ko ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Akt Activation ◽  
Peripheral Insulin Resistance ◽  
Diet Induced Obesity

ABSTRACT Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH2-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1 − / − mice are protected against HFD-induced obesity and insulin resistance. Here we show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD-induced obesity. However, muscle-specific JNK1-deficient (MKO) mice exhibit improved insulin sensitivity compared with control wild-type (MWT) mice. Thus, insulin-stimulated AKT activation is suppressed in muscle, liver, and adipose tissue of HFD-fed MWT mice but is suppressed only in the liver and adipose tissue of MKO mice. These data demonstrate that JNK1 in muscle contributes to peripheral insulin resistance in response to diet-induced obesity.

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