Targeting PLD2 in adipocytes augments adaptive thermogenesis by improving mitochondrial quality and quantity in mice

2021 ◽  
Vol 219 (2) ◽  
Author(s):  
Hyung Sik Kim ◽  
Min Young Park ◽  
Nam Joo Yun ◽  
Hye Sun Go ◽  
Mi Young Kim ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Specific Inhibitor ◽  
Adaptive Thermogenesis ◽  
Diet Induced Obesity ◽  
Diet Induced Thermogenesis ◽  
And Migration

Phospholipase D (PLD)2 via its enzymatic activity regulates cell proliferation and migration and thus is implicated in cancer. However, the role of PLD2 in obesity and type 2 diabetes has not previously been investigated. Here, we show that during diet-induced thermogenesis and obesity, levels of PLD2 but not PLD1 in adipose tissue are inversely related with uncoupling protein 1, a key thermogenic protein. We demonstrate that the thermogenic program in adipose tissue is significantly augmented in mice with adipocyte-specific Pld2 deletion or treated with a PLD2-specific inhibitor and that these mice are resistant to high fat diet–induced obesity, glucose intolerance, and insulin resistance. Mechanistically, we show that Pld2 deletion in adipose tissue or PLD2 pharmacoinhibition acts via p62 to improve mitochondrial quality and quantity in adipocytes. Thus, PLD2 inhibition is an attractive therapeutic approach for obesity and type 2 diabetes by resolving defects in diet-induced thermogenesis.

scholarly journals RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2014 ◽  
Vol 224 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Xiao-Bing Cui ◽  
Jun-Na Luan ◽  
Jianping Ye ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Tolerance Test ◽  
High Fat ◽  
Diet Induced Obesity

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32−/− (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32−/− mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32−/− induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.

scholarly journals Inflammation of adipose tissue. Part 2. Pathogenetic role in type 2 diabetes mellitus

2009 ◽  
Vol 55 (5) ◽  
pp. 43-48 ◽  
Author(s):  
V Shvarts
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Cell Function ◽  
Signal Pathway ◽  
Insulin Signal ◽  
Kinase Cascade

This review deals with the role of adipose tissue inflammation (ATI) in the development of type 2 diabetes mellitus (DM2). ATI is regarded as a link between obesity and DM2. The review illustrates the involvement of main adipokines in pathogenesis of DM2 and provides a detailed description of such factors as impaired adiponectin and stimulation of cytokine production responsible for metabolic disorders, activation of lipolysis, in adipocytes, increased fatty acid and triglyceride levels, suppression of insulin activity at the receptor and intracellular levels. Adipokines, in the first place cytokines, act on the insulin signal pathway and affect the intracellular inflammatory kinase cascade. At the intercellular level, ATI stimulates JNK and IKK-beta/kB responsible for the development of insulin resistance via such mechanisms as activation of cytokine secretion in the adipose tissue, oxidative stress, and induction of endoplasmic reticulum enzymes. The key role of JNK and IKK-beta/kB in the inhibition of the insulin signal pathway is mediated through inactivation of insulin receptor substrate 1. Also, it is shown that ATI modulates B-cell function and promotes progressive reduction of insulin secretion.

scholarly journals Functional Interactomes of Genes Showing Association with Type-2 Diabetes and Its Intermediate Phenotypic Traits Point towards Adipo-Centric Mechanisms in Its Pathophysiology

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 601
Author(s):  
Aditya Saxena ◽  
Nitin Wahi ◽  
Anshul Kumar ◽  
Sandeep Kumar Mathur
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Network Analysis ◽  
Potential Role ◽  
Phenotypic Traits ◽  
Protein Protein Interaction ◽  
Cellular Processes ◽  
Antidiabetic Treatment

The pathogenic mechanisms causing type 2 diabetes (T2D) are still poorly understood; a greater awareness of its causation can lead to the development of newer and better antidiabetic drugs. In this study, we used a network-based approach to assess the cellular processes associated with protein–protein interaction subnetworks of glycemic traits—HOMA-β and HOMA-IR. Their subnetworks were further analyzed in terms of their overlap with the differentially expressed genes (DEGs) in pancreatic, muscle, and adipose tissue in diabetics. We found several DEGs in these tissues showing an overlap with the HOMA-β subnetwork, suggesting a role of these tissues in β-cell failure. Many genes in the HOMA-IR subnetwork too showed an overlap with the HOMA-β subnetwork. For understanding the functional theme of these subnetworks, a pathway-to-pathway complementary network analysis was done, which identified various adipose biology-related pathways, containing genes involved in both insulin secretion and action. In conclusion, network analysis of genes showing an association between T2D and its intermediate phenotypic traits suggests their potential role in beta cell failure. These genes enriched the adipo-centric pathways and were expressed in both pancreatic and adipose tissue and, therefore, might be one of the potential targets for future antidiabetic treatment.

scholarly journals Adipose Tissue-Derived Signatures for Obesity and Type 2 Diabetes: Adipokines, Batokines and MicroRNAs

2019 ◽  
Vol 8 (6) ◽  
pp. 854 ◽  
Author(s):  
Min-Woo Lee ◽  
Mihye Lee ◽  
Kyoung-Jin Oh
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Metabolic Disturbances ◽  
Endocrine Organ ◽  
Brown Adipose ◽  
Exosomal Mirnas ◽  
Exosomal Mirna

Obesity is one of the main risk factors for type 2 diabetes mellitus (T2DM). It is closely related to metabolic disturbances in the adipose tissue that primarily functions as a fat reservoir. For this reason, adipose tissue is considered as the primary site for initiation and aggravation of obesity and T2DM. As a key endocrine organ, the adipose tissue communicates with other organs, such as the brain, liver, muscle, and pancreas, for the maintenance of energy homeostasis. Two different types of adipose tissues—the white adipose tissue (WAT) and brown adipose tissue (BAT)—secrete bioactive peptides and proteins, known as “adipokines” and “batokines,” respectively. Some of them have beneficial anti-inflammatory effects, while others have harmful inflammatory effects. Recently, “exosomal microRNAs (miRNAs)” were identified as novel adipokines, as adipose tissue-derived exosomal miRNAs can affect other organs. In the present review, we discuss the role of adipose-derived secretory factors—adipokines, batokines, and exosomal miRNA—in obesity and T2DM. It will provide new insights into the pathophysiological mechanisms involved in disturbances of adipose-derived factors and will support the development of adipose-derived factors as potential therapeutic targets for obesity and T2DM.

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 Important role of fat tissue hormones in development of comorbid chronic pancreatitis and obesity

2017 ◽  
Vol 37 (3) ◽  
pp. 30-35
Author(s):  
T. N. Hristich
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adipose Tissue ◽  
Chronic Pancreatitis ◽  
Pancreatic Disease ◽  
Pancreatic Tissue ◽  
Visceral Adipose

Aim of this paper is to consider the role of hormones of the adipose tissue in mechanisms of obesity, metabolic syndrome, type 2 diabetes mellitus upon chronic pancreatitis. Materials and methods. The literature review indicates the value of visceral fat in the development of insulin resistance, dyslipidemia, including atherogenic one, taking into account the possible infiltration of pancreatic tissue by adipocytes. Participation of some adipocytokines of adipose tissue in the development of obesity upon chronic pancreatitis is highlighted. It is shown that in some cases the hormones of visceral adipose tissue, penetrating through the portal vein to the liver and then to the pancreas, aggravated the course of systemic chronic inflammation of the inherent chronic pancreatitis, promote steatosis and development of fatty pancreatic disease. Conclusion. Literary sources indicate the leading role of visceral adipose tissue and its hormones in the formation of obesity in chronic pancreatitis. Due to the infiltration of the pancreatic tissue by adipocytes, lipoidosis and steatosis develop. With the progression of the process type 2 diabetes mellitus, fatty liver or pancreatic disease, or cancer of these orhans. Consequently, there is a need for serious differentiated preventive and curative measures aimed at promoting a healthy lifestyle to improve the quality of life of patients suffering from chronic pancreatitis.

scholarly journals Significant role of fat tissue hormones in development of comorbid chronic pancreatitis and obesity

2018 ◽  
Vol 39 (1) ◽  
pp. 4-9
Author(s):  
T. N. Hristich
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Chronic Pancreatitis ◽  
Visceral Adipose Tissue ◽  
Healthy Lifestyle ◽  
Pancreatic Disease ◽  
Pancreatic Tissue ◽  
Visceral Adipose

Aim is to consider the role of hormones in the adipose tissue of obesity mechanisms of metabolic syndrome, type 2 diabetes mellitus in chronic pancreatitis. Materials and methods. Literature review indicates the value of visceral fat in the development of insulin resistance, dyslipidemia, including atherogenic one, taking into account the possible infiltration of pancreatic tissue by adipocytes. Participation of some adipocytokines of adipose tissue in the development of obesity in chronic pancreatitis is highlighted. It is shown that in some cases the hormones of visceral adipose tissue, penetrating through the portal vein to the liver and then to the pancreas, aggravated the course of systemic chronic inflammation typical for the inherent chronic pancreatitis, formed steatosis and promoted development of fatty disease of the pancreas. Conclusion. Literary sources show the leading role of visceral adipose tissue and its hormones in the formation of obesity in chronic pancreatitis. Lipoidosis or steatosis develop due to the infiltration of the liver and pancreatic tissue by adipocytes. Upon the progression of the type 2 diabetes, fatty liver or pancreatic disease, or cancer of these organs may develop. Consequently, there is a strong need for a serious differentiated preventive and curative measures aimed at promoting a healthy lifestyle to improve the quality of life of patients suffering from chronic pancreatitis.

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.

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