Nascent Protein Labeling Strategy Disclosed Mitochondrial Proteomic Response in Punicalagin Intervened Insulin Resistance of HepG2 Cells

2022 ◽  
Author(s):  
Zhengyi Zhang ◽  
Mengqi Zeng ◽  
Xiao Han ◽  
Zhanwu Hou ◽  
Zhen Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Hepg2 Cells ◽  
Metabolic Diseases ◽  
Protein Labeling ◽  
Obesity And Diabetes ◽  
The Common ◽  
Proteomic Response

Insulin Resistance (IR), as the common pathophysiological basis, is closely related to a variety of metabolic diseases, such as obesity and diabetes. IR is often accompanied with mitochondrial dysfunction which...

Abstract P233: Diabetic Cardiomyopathy is Reversed by Increased Mitochondrial Bioenergetics Due to PGC-1α Activation by EET Treatment of Obese Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Jian Cao ◽  
John A McClung ◽  
Shailendra P Singh ◽  
Lars Bellner ◽  
Maayan Waldman ◽  
...  
Keyword(s):  
Heart Failure ◽  
Insulin Resistance ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Systolic Function ◽  
Control Group ◽  
Protein Markers ◽  
Obesity And Diabetes

Introduction: Obesity and diabetes are associated with progressive cardiac fibrosis that, sequentially, results in diastolic dysfunction, reduced contractility, and ultimately heart failure. Contributing factors include hyperglycemia, insulin resistance, mitochondrial dysfunction, and a reduction in AMPK signaling. PGC-1α activates mitochondrial biogenesis and oxidative phosphorylation and is decreased in patients with diabetes mellitus (DM). We hypothesize that an epoxyeicosatrienoic acids (EETs) agonist (EET-A) will increase PGC-1α levels in a db mouse model of DM attenuate cardiomyopathy, and prevent heart failure. Methods: Db mice (4-wks), were allowed to acclimatize for 16-wks and were then divided into 3 treatment groups for an additional 16 wks: A) control, B) EET-A 1.5mg/100g BW 2 weeks and C) EET-A-Ln-PGC-1α shRNA. Ln-PGC-1α shRNA suppressed PGC-1α protein in heart tissue by 40-50%. Oxygen consumption (VO 2 ), and blood glucose was determined. Heart tissues were harvested to measure PGC-1α, HO-1, pAMPK, PGC-1α, echocardiographic fractional shortening, mitochondrial oxidative phosphorylation (OXPHOS) and mitofusion protein markers. Results: All mice developed heart failure by the end of 16 weeks and were characterized by a decrease in myocardial contractility, an increase in insulin resistance and blood pressure, decreased VO 2 , the appearance of mitochondria dysfunction and a decrease in AMPK and downstream PGC-1α signaling. Mice treated with EET-A demonstrated an increase in PGC-1α levels, improved mitochondrial function and oxidative phosphorylation (p<0.01 vs control), increased NO bioavailability (p<0.05 vs control), and normalization of glucose metabolism, insulin levels, VO 2 and LV systolic function (p<0.05 vs control). All of these findings were suppressed by PGC-1α inhibition which was accompanied by the onset of even more severe LV dysfunction than in the control group. Conclusion: Increased EET levels result in activation of PGC-1α-HO-1 which reverses diabetes induced insulin resistance, mitochondrial dysfunction, and cardiomyopathy. EET may have potential as a powerful agent for therapeutic application in the treatment of diabetic cardiomyopathy.

(‐)‐Epigallocatechin‐3‐gallate Ameliorates Insulin Resistance and Mitochondrial Dysfunction in HepG2 Cells: Involvement of Bmal1

2017 ◽  
Vol 61 (12) ◽  
pp. 1700440 ◽  
Author(s):  
Yashi Mi ◽  
Guoyuan Qi ◽  
Yuqi Gao ◽  
Runnan Li ◽  
Yiwen Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Hepg2 Cells

scholarly journals Mitochondrial Dysfunction and Diabetes: Is Mitochondrial Transfer a Friend or Foe?

Biology ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 33 ◽  
Author(s):  
Magdalene K Montgomery
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Association Studies ◽  
Metabolic Status ◽  
Genetic Manipulations ◽  
Physiological Importance ◽  
Metabolic Defects ◽  
Obesity And Diabetes ◽  
Mitochondrial Transfer

Obesity, insulin resistance and type 2 diabetes are accompanied by a variety of systemic and tissue-specific metabolic defects, including inflammation, oxidative and endoplasmic reticulum stress, lipotoxicity, and mitochondrial dysfunction. Over the past 30 years, association studies and genetic manipulations, as well as lifestyle and pharmacological invention studies, have reported contrasting findings on the presence or physiological importance of mitochondrial dysfunction in the context of obesity and insulin resistance. It is still unclear if targeting mitochondrial function is a feasible therapeutic approach for the treatment of insulin resistance and glucose homeostasis. Interestingly, recent studies suggest that intact mitochondria, mitochondrial DNA, or other mitochondrial factors (proteins, lipids, miRNA) are found in the circulation, and that metabolic tissues secrete exosomes containing mitochondrial cargo. While this phenomenon has been investigated primarily in the context of cancer and a variety of inflammatory states, little is known about the importance of exosomal mitochondrial transfer in obesity and diabetes. We will discuss recent evidence suggesting that (1) tissues with mitochondrial dysfunction shed their mitochondria within exosomes, and that these exosomes impair the recipient’s cell metabolic status, and that on the other hand, (2) physiologically healthy tissues can shed mitochondria to improve the metabolic status of recipient cells. In this context the determination of whether mitochondrial transfer in obesity and diabetes is a friend or foe requires further studies.

scholarly journals Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications

2013 ◽  
Vol 305 (6) ◽  
pp. E679-E686 ◽  
Author(s):  
Kashif M. Munir ◽  
Sruti Chandrasekaran ◽  
Feng Gao ◽  
Michael J. Quon
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Functional Foods ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Clinical Medicine ◽  
Cardiovascular Complications ◽  
Therapeutic Implications ◽  
Obesity And Diabetes ◽  
Cardiovascular Morbidity And Mortality

The rising epidemic of diabetes is a pressing issue in clinical medicine worldwide from both healthcare and economic perspectives. This is fueled by overwhelming increases in the incidence and prevalence of obesity. Obesity and diabetes are characterized by both insulin resistance and endothelial dysfunction that lead to substantial increases in cardiovascular morbidity and mortality. Reciprocal relationships between insulin resistance and endothelial dysfunction tightly link metabolic diseases including obesity and diabetes with their cardiovascular complications. Therefore, therapeutic approaches that target either insulin resistance or endothelial dysfunction alone are likely to simultaneously improve both metabolic and cardiovascular pathophysiology and disease outcomes. Moreover, combination therapies with agents targeting distinct mechanisms are likely to have additive or synergistic benefits. Conventional therapies for diabetes and its cardiovascular complications that are both safe and effective are insufficient to meet rising demand. Large, robust, epidemiologic studies demonstrate beneficial metabolic and cardiovascular health effects for many functional foods containing various polyphenols. However, precise molecular mechanisms of action for food polyphenols are largely unknown. Moreover, translation of these insights into effective clinical therapies has not been fully realized. Nevertheless, some functional foods are likely sources for safe and effective therapies and preventative strategies for metabolic diseases and their cardiovascular complications. In this review, we emphasize recent progress in elucidating molecular, cellular, and physiological actions of polyphenols from green tea (EGCG), cocoa (ECG), and citrus fruits (hesperedin) that are related to improving metabolic and cardiovascular pathophysiology. We also discuss a rigorous comprehensive approach to studying functional foods that is essential for developing novel, effective, and safe medications derived from functional foods that will complement existing conventional drugs.

scholarly journals Characterization of the ZDSD Rat: A Translational Model for the Study of Metabolic Syndrome and Type 2 Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Richard G. Peterson ◽  
Charles V. Jackson ◽  
Karen Zimmerman ◽  
Willem de Winter ◽  
Norman Huebert ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Metabolic Diseases ◽  
Oral Glucose ◽  
Glucose Levels ◽  
Zdf Rat ◽  
Obesity And Diabetes ◽  
Elevated Glucose ◽  
Polygenic Obesity

Metabolic syndrome and T2D produce significant health and economic issues. Many available animal models have monogenic leptin pathway mutations that are absent in the human population. Development of the ZDSD rat model was undertaken to produce a model that expresses polygenic obesity and diabetes with an intact leptin pathway. A lean ZDF rat with the propensity for beta-cell failure was crossed with a polygenetically obese Crl:CD (SD) rat. Offspring were selectively inbred for obesity and diabetes for >30 generations. In the current study, ZDSD rats were followed for 6 months; routine clinical metabolic endpoints were included throughout the study. In the prediabetic metabolic syndrome phase, ZDSD rats exhibited obesity with increased body fat, hyperglycemia, insulin resistance, dyslipidemia, glucose intolerance, and elevated HbA1c. As disease progressed to overt diabetes, ZDSD rats demonstrated elevated glucose levels, abnormal oral glucose tolerance, increases in HbA1c levels, reductions in body weight, increased insulin resistance with decreasing insulin levels, and dyslipidemia. The ZDSD rat develops prediabetic metabolic syndrome and T2D in a manner that mirrors the development of metabolic syndrome and T2D in humans. ZDSD rats will provide a novel, translational animal model for the study of human metabolic diseases and for the development of new therapies.

scholarly journals Molecular Insulin Actions Are Sexually Dimorphic in Lipid Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Rosa Isela Ortiz-Huidobro ◽  
Myrian Velasco ◽  
Carlos Larqué ◽  
Rene Escalona ◽  
Marcia Hiriart
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Sexual Dimorphism ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Critical Role ◽  
Metabolic Dysfunction ◽  
Anabolic Hormone ◽  
Obesity And Diabetes

The increment in energy-dense food and low physical activity has contributed to the current obesity pandemic, which is more prevalent in women than in men. Insulin is an anabolic hormone that regulates the metabolism of lipids, carbohydrates, and proteins in adipose tissue, liver, and skeletal muscle. During obesity, nutrient storage capacity is dysregulated due to a reduced insulin action on its target organs, producing insulin resistance, an early marker of metabolic dysfunction. Insulin resistance in adipose tissue is central in metabolic diseases due to the critical role that this tissue plays in energy homeostasis. We focused on sexual dimorphism on the molecular mechanisms of insulin actions and their relationship with the physiology and pathophysiology of adipose tissue. Until recently, most of the physiological and pharmacological studies were done in males without considering sexual dimorphism, which is relevant. There is ample clinical and epidemiological evidence of its contribution to the establishment and progression of metabolic diseases. Sexual dimorphism is a critical and often overlooked factor that should be considered in design of sex-targeted therapeutic strategies and public health policies to address obesity and diabetes.

scholarly journals Is Mitochondrial Dysfunction a Common Root of Noncommunicable Chronic Diseases?

2020 ◽  
Vol 41 (3) ◽  
pp. 491-517 ◽  
Author(s):  
Alexis Diaz-Vegas ◽  
Pablo Sanchez-Aguilera ◽  
James R Krycer ◽  
Pablo E Morales ◽  
Matías Monsalves-Alvarez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Dysfunction ◽  
Chronic Diseases ◽  
Metabolic Diseases ◽  
State Of The Art ◽  
Mitochondrial Damage ◽  
Targeted Therapeutics ◽  
Common Root

Abstract Mitochondrial damage is implicated as a major contributing factor for a number of noncommunicable chronic diseases such as cardiovascular diseases, cancer, obesity, and insulin resistance/type 2 diabetes. Here, we discuss the role of mitochondria in maintaining cellular and whole-organism homeostasis, the mechanisms that promote mitochondrial dysfunction, and the role of this phenomenon in noncommunicable chronic diseases. We also review the state of the art regarding the preclinical evidence associated with the regulation of mitochondrial function and the development of current mitochondria-targeted therapeutics to treat noncommunicable chronic diseases. Finally, we give an integrated vision of how mitochondrial damage is implicated in these metabolic diseases.

scholarly journals Leptin as a Potential Regulator of FGF21

2016 ◽  
Vol 38 (3) ◽  
pp. 1218-1225 ◽  
Author(s):  
Mohamed Asrih ◽  
Christelle Veyrat-Durebex ◽  
Anne-Laure Poher ◽  
Jacqueline Lyautey ◽  
Françoise Rohner-Jeanrenaud ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepg2 Cells ◽  
Wistar Rats ◽  
Metabolic Diseases ◽  
Fibroblast Growth Factor 21 ◽  
New Findings ◽  
Expression Site ◽  
Fgf21 Expression

Background/Aims: Fibroblast growth factor 21 (FGF21), a potent metabolic regulator, has been shown to improve insulin sensitivity in animal models of insulin resistance. Several studies have focused on identifying mediators of FGF21 effects. However, the identification of factors involved in FGF21 regulation is far from complete. As leptin is a potent metabolic modulator as well, we aimed at characterizing whether leptin may regulate FGF21. Methods: We investigated a potential regulation of FGF21 by leptin in vivo in Wistar rats and in vitro using human derived hepatocarcinoma HepG2 cells. This model was chosen as the liver is considered the main FGF21 expression site. Results: We found that leptin injections increased plasma FGF21 levels in adult Wistar rats. This was confirmed in vitro, as leptin increased FGF21 expression in HepG2 cells. We also showed that the leptin effect on FGF21 expression was mediated by STAT3 activation in HepG2 cells. Conclusion: New findings regarding a leptin-STAT3-FGF21 axis were provided in this study, although investigating the exact mechanisms linking leptin and FGF21 are still needed. These results are of great interest in the context of identifying potential new clinical approaches to treat metabolic diseases associated with insulin resistance, such as obesity and type 2 diabetes.

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