scholarly journals IF1 connects obesity and insulin resistance through mitochondrial reprogramming in association with ANT2

2020 ◽  
Author(s):  
Ying Wang ◽  
Yaya Guan ◽  
Jiaojiao Zhang ◽  
Xinyu Cao ◽  
Shuang Shen ◽  
...  
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Nuclear Dna ◽  
Maximal Oxygen Consumption ◽  
Atp Synthesis ◽  
Tissue Growth ◽  
Chow Diet ◽  
Colon Tissue ◽  
Compensatory Response ◽  
Atp Production

AbstractIF1 (ATPIF1) is a nuclear DNA-encoded protein with an activity in the inhibition of catalytic activity of F1Fo-ATP synthase (ATPase), an enzyme for ATP synthesis in mitochondria. A role of IF1 remains unknown in the metabolic disorder in obesity. In this study, IF1 was examined in the diet-induced obese (DIO) mice and a decrease in IF1 protein was observed in several tissues including the skeletal muscle, liver and intestine in the absence of mRNA alteration. Significance of the reduction was investigated in the IF1-KO mice, in which insulin sensitivity was improved in the absence of body weight alteration on Chow diet. On a high fat diet (HFD), the IF1-KO mice gain more body weight as a result of enhanced fat tissue growth. The energy expenditure and locomotion activity were decreased in the KO mice without an alteration in food intake. The increase in insulin sensitivity remained in the obese KO mice. The colon tissue exhibited a resistance to the HFD-induced atrophy with less cell apoptosis and more secretion of GLP-1. Mitochondria exhibited an enhanced ATP production and maximal oxygen consumption without an alteration in the respiratory chain proteins. However, the ATP level was reduced in the fasting condition in the muscle as well as the liver. Mitophagy was enhanced with elevated accumulation of PINK1 and Parkin proteins in the mitochondria. The protein abundance of ADP/ATP translocase 2 (ANT2) was decreased in the inner membrane of mitochondria to account for the reduced apoptosis and enhanced mitophagy. The data suggest that the IF1 reduction in obesity leads to reprogramming of mitochondrial metabolism in a compensatory response to maintain the insulin sensitivity through down-regulation of ANT2 protein.

scholarly journals A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance

2011 ◽  
Vol 301 (5) ◽  
pp. E825-E835 ◽  
Author(s):  
Lucy S. Jun ◽  
C. Parker Siddall ◽  
Evan D. Rosen
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Intolerance ◽  
High Fat Diet ◽  
Metabolic Phenotype ◽  
Chow Diet ◽  
High Fat

Adipose tissue controls energy homeostasis and systemic insulin sensitivity through the elaboration of a series of cytokines and hormones, collectively termed “adipokines.” We and others have identified Lcn2 as a novel adipokine, but its exact role in obesity-induced insulin resistance remains controversial. The aim of this study was to examine the metabolic phenotype of Lcn2−/− mice to clarify the role of Lcn2 in metabolism. Male and female Lcn2−/− and wild-type (WT) littermates were placed on either chow or high-fat diet (HFD) to characterize their metabolic phenotype. Studies included body weight and body composition, glucose and insulin tolerance tests, and adipokine expression studies in serum and in white adipose tissue (WAT). Neither chow nor HFD cohorts showed any differences in body weight or body composition. Chow-fed Lcn2−/− mice did not exhibit any difference in glucose homeostasis compared with WT mice. Fasting serum glucose levels were lower in the chow-fed Lcn2−/− mice, but this finding was not seen in the HFD cohort. Serum adiponectin, leptin, resistin, and RBP4 levels were not different between WT and Lcn2−/− on chow diet. HFD-fed male Lcn2−/− mice did display a small improvement in glucose tolerance, but no difference in insulin sensitivity was seen in either male or female Lcn2−/− mice on HFD. We conclude that the global ablation of Lcn2 has a minimal effect on obesity-associated glucose intolerance but does not appear to affect either age- or obesity-mediated insulin resistance in vivo.

scholarly journals MITOCHONDRIAL DISEASE THERAPY

2021 ◽  
pp. 24-30
Author(s):  
KANIKA KHAJURIA ◽  
VIJAY KHAJURIA ◽  
VINEETA SAWHNEY
Keyword(s):  
Mitochondrial Dysfunction ◽  
Nuclear Dna ◽  
Mitochondrial Diseases ◽  
Atp Synthesis ◽  
Atp Production ◽  
Complex Disorders ◽  
Disease Therapy ◽  
Biogenesis Of Mitochondria ◽  
Beneficial Outcome

Mitochondria perform number of important functions, including synthesis of adenosine triphosphate (ATP) and generation of reactive oxygen species (ROS). Most of the organs depend on ATP to perform. Therefore, in depleted or dysfunctional mitochondrial states, there is less energy production coupled with the accumulation of oxidants. Oxidative stress is involved in the pathophysiology of various disorders especially involving neurons and the cardiovascular system. Mitochondrial diseases are a clinically heterogeneous group of disorders resulting from either inherited or spontaneous mutations in mitochondrial deoxyribonucleic acid (mtDNA) or nuclear DNA. In primary mitochondrial dysfunction disease, the mutation affects the oxidative phosphorylation (OXPHOS) functioning, while secondary mitochondrial dysfunction does not involve OXPHOS genes. Since mutations of genes are involved, therefore, therefore the mitochondrial dysfunctional states are not easy to treat. However, number of strategies that lead to increase ATP production, counter ROS facilitates improvement. The current strategy is to focus on stimulating the biogenesis of mitochondria, antioxidants, and cofactors to enhance ATP synthesis. The role of non-pharmaceuticals cannot be underestimated either. The exercise, diet, and environment influence have well-established beneficial outcome in these disorders. Gene therapy holds promise in the future management of these complex disorders.

scholarly journals 252 Combined soluble fiber improve the obesity phenotype and insulin sensitivity of diet-induced obese mice by regulating the intestinal microbial composition

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 69-69
Author(s):  
Chuanhui Xu ◽  
Jianhua Liu ◽  
Rong Zheng ◽  
Jian Peng
Keyword(s):  
Insulin Sensitivity ◽  
Feed Intake ◽  
Short Chain Fatty Acids ◽  
Control Group ◽  
Chow Diet ◽  
Rrna Gene ◽  
Soluble Fiber ◽  
Colon Tissue ◽  
Microbial Composition ◽  
Period 2

Abstract With the global spread of obesity, we recognize the importance of healthy diet and it is necessary to increase the dietary fiber intake. To investigate the effects of the combined soluble fiber (CSF) on the health of obese individuals, we divided 14 obese C57BL/6J male mice into two groups: Control group (n = 7) and CSF group (n = 7). Both groups received a 12-week high-fat diet (Period 1) and a 4-week low-fat chow diet (Period 2), but CSF was added into diets for the CSF group and equivalently replaced for cellulose. Compared with the Control group, the CSF group maintained a similar body weight and feed intake, but had higher insulin sensitivity, during the period 1. During the period 2, both groups lost weight, but the CSF group lost more weight, and decreased the Lee’s index as well as the daily feed intake, improved the insulin sensitivity. The CSF group increased the levels of PYY and GLP-1 in the postprandial blood, and increased the level of adiponectin while decreased the levels of endotoxin, leptin, interleukin-6 and TNF-α in the fasting blood. The CSF group increased mucosal layer thickness, crypt length and Brdu positive cell rate of the colon tissue. Stool samples were collected at the 16th week and analyzed with 16s rRNA gene sequencing. Results indicated that the CSF group reduced the relative abundance of the phyla Proteobacteria and Firmicutes, while increased Bacteroides and the Bacteroides/Firmicutes ratio. CSF group had higher levels of acetic acid, propionic acid and total short-chain fatty acids (SCFAs) in stool. These results suggest that CSF may promote the production of SCFAs by regulating intestinal microbial composition, promote the releases of satiety hormones, thereby reducing feed intake. On the other hand, CSF improves the intestinal integrity, reduces inflammation, and then improve insulin sensitivity.

The Important Roles of Matrix Metalloproteinases in the Pathophysiology of Obesity

2017 ◽  
Vol 68 (7) ◽  
pp. 1481-1484 ◽  
Author(s):  
Radu Mihail Mirica ◽  
Mihai Ionescu ◽  
Alexandra Mirica ◽  
Octav Ginghina ◽  
Razvan Iosifescu ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Matrix Metalloproteinases ◽  
English Language ◽  
Critical Role ◽  
Animal Experiments ◽  
Hdl Cholesterol ◽  
Tissue Growth ◽  
Basement Membranes ◽  
Body Weight Reduction

Obesity involves the growth of adipose tissue cells (adipocytes and preadipocytes), as well as microvascular endothelial cells. Matrix metalloproteinases (MMPs) are relevant ezymes for the modulation of extracellular matrix (ECM) and adipocyte and preadipocytes differentiation. They are elevated in obese patients, generating abnormal ECM metabolism.[1]. This article proposes a thorough study of literature with focus on the important roles of matrix metalloproteinases in the pathophysiology of obesity. The article represents a narrative review based on an English-language PubMed research of the medical literature regardind important aspects of the proposed aim. MMP-2 activity was signi�cantly higher than MMP-9, both activities were detectable. MMP-9 was strongly correlated with body weight parameters before surgery, as well as after significant body weight reduction as a result of bariatric surgery. Concerning MMP-2 and MMP-9 they are also involved in the turnover of basement membranes both those of adipose tissue and endothelial. MMP-9 levels were moderately correlated with HDL cholesterol levels. Taken together, the present data suggest that changes in ECM through MMP-mediated degradation might play a critical role in the adipocyte differentiation process. These findings are detected both in clinical trials and in laboratory animal experiments. It is then tempting to speculate that the adipocyte-derived MMPs might represent a new pharmacological target for the inhibition of adipose tissue growth by inhibiting adipose differentiation as well as angiogenic process.

scholarly journals Human Trisomic iPSCs from Down Syndrome Fibroblasts Manifest Mitochondrial Alterations Early during Neuronal Differentiation

Biology ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 609
Author(s):  
Nunzia Mollo ◽  
Matteo Esposito ◽  
Miriam Aurilia ◽  
Roberta Scognamiglio ◽  
Rossella Accarino ◽  
...  
Keyword(s):  
Down Syndrome ◽  
Mitochondrial Dysfunction ◽  
Neuronal Differentiation ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Atp Synthesis ◽  
Differentiation Markers ◽  
Differentiation Potential ◽  
Atp Production ◽  
Mitochondrial Alterations

Background: The presence of mitochondrial alterations in Down syndrome suggests that it might affect neuronal differentiation. We established a model of trisomic iPSCs, differentiating into neural precursor cells (NPCs) to monitor the occurrence of differentiation defects and mitochondrial dysfunction. Methods: Isogenic trisomic and euploid iPSCs were differentiated into NPCs in monolayer cultures using the dual-SMAD inhibition protocol. Expression of pluripotency and neural differentiation genes was assessed by qRT-PCR and immunofluorescence. Meta-analysis of expression data was performed on iPSCs. Mitochondrial Ca2+, reactive oxygen species (ROS) and ATP production were investigated using fluorescent probes. Oxygen consumption rate (OCR) was determined by Seahorse Analyzer. Results: NPCs at day 7 of induction uniformly expressed the differentiation markers PAX6, SOX2 and NESTIN but not the stemness marker OCT4. At day 21, trisomic NPCs expressed higher levels of typical glial differentiation genes. Expression profiles indicated that mitochondrial genes were dysregulated in trisomic iPSCs. Trisomic NPCs showed altered mitochondrial Ca2+, reduced OCR and ATP synthesis, and elevated ROS production. Conclusions: Human trisomic iPSCs can be rapidly and efficiently differentiated into NPC monolayers. The trisomic NPCs obtained exhibit greater glial-like differentiation potential than their euploid counterparts and manifest mitochondrial dysfunction as early as day 7 of neuronal differentiation.

scholarly journals Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5390
Author(s):  
Qianhui Zeng ◽  
Nannan Wang ◽  
Yaru Zhang ◽  
Yuxuan Yang ◽  
Shuangshuang Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Glycolipid Metabolism ◽  
Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

scholarly journals Chronic photoperiodic manipulation induced chronodisruption upregulates HSP60 during early pro-atherogenic remodeling in thoracic aorta of C57BL/6J mice

2021 ◽  
Vol 82 (1) ◽  
Author(s):  
Kavita Shirsath ◽  
Apeksha Joshi ◽  
Aliasgar Vohra ◽  
Ranjitsinh Devkar
Keyword(s):  
Body Weight ◽  
Thoracic Aorta ◽  
Serum Lipid ◽  
Body Weight Gain ◽  
Hdl Cholesterol ◽  
Circadian Disruption ◽  
Control Group ◽  
Chow Diet ◽  
Heat Shock Protein 60 ◽  
Lipid Parameters

Abstract Background Circadian disruption is often associated with aggravation of atherosclerosis; however, the pathophysiological mechanisms underlying atherogenic initiation in normolipidemic diet remains unclear. Most of the studies done for understanding circadian disruption induced atherosclerosis have been carried out in murine model of hyperlipidemia induced atherosclerosis. The present study investigates pro-atherogenic events in response to chronic photoperiodic manipulation induced chronodisruption (PMCD) in C57BL/6J mice fed with laboratory chow diet. Results The results were compared with atherogenic initiation induced by high fat high fructose (HFHF) diet. The combined effects of HFHF and PMCD on atherogenic initiation were also investigated for possible synergy of both variants. The HFHF and HFHF+PMCD groups recorded increments in body weight gains and serum lipid parameters (TC, TG, LDL-cholesterol, VLDL) and a decrement in HDL-cholesterol as compared to the control group. However, PMCD group recorded body weight gain similar to that of the control group, but the serum lipid parameters (TG and VLDL) were significantly elevated and the HDL levels were lowered. However, prominent hypertrophic remodeling, higher collagen deposition, and elastin derangement, along with endothelial dysfunction, its activation, and macrophage infiltration, were observed in thoracic aorta of all the three experimental groups. But the mRNA and immunoblots of heat shock protein 60 (HSP60) in thoracic aorta was found to be maximum in PMCD followed by HFHF and HFHF+PMCD groups. Conclusion Laboratory chow feeding coupled with photoperiodic manipulation mediated chronodisruption overexpress HSP60 that in turn plays a central role in PMCD mediated pro-atherogenic remodeling in thoracic aorta of C57BL/6J mice.

scholarly journals Effects of body weight and alcohol consumption on insulin sensitivity

2010 ◽  
Vol 9 (1) ◽  
Author(s):  
Qiwei X Paulson ◽  
Jina Hong ◽  
Valerie B Holcomb ◽  
Nomeli P Nunez
Keyword(s):  
Body Weight ◽  
Insulin Sensitivity ◽  
Alcohol Consumption

Effects of cortisol and progesterone on insulin binding and lipogenesis in adipocytes from normal and diabetic rats

1985 ◽  
Vol 106 (2) ◽  
pp. 225-231 ◽  
Author(s):  
A.-M. Mendes ◽  
R. J. Madon ◽  
D. J. Flint
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Receptor ◽  
Body Weight Gain ◽  
Serum Insulin ◽  
Insulin Binding ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Receptor Concentration

ABSTRACT Cortisol implants in normal and diabetic rats reduced body weight, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in isolated adipocytes, whilst insulin sensitivity was unchanged. In normal but not diabetic rats these changes were accompanied by increased serum glucose and insulin concentrations. In contrast, progesterone implants in normal and diabetic rats increased body weight gain, adiposity, insulin receptor concentration and both basal and insulin-stimulated rates of lipogenesis in adipose tissue, again without affecting insulin sensitivity. Progesterone did not affect serum insulin concentrations in normal or diabetic rats but accelerated the decline in serum glucose concentrations which occurred during an overnight fast in diabetic rats. The results suggest that (1) cortisol inhibits lipogenesis in adipose tissue without affecting insulin sensitivity, (2) cortisol reduces insulin binding in adipose tissue without a requirement for hyperinsulinaemia, which might itself indirectly lead to down-regulation of the insulin receptor, and (3) in diabetic rats progesterone stimulates lipogenesis in adipose tissue without any increase in food intake or serum insulin concentrations suggesting that progesterone may have a direct anabolic role in adipose tissue. J. Endocr. (1985) 106, 225–231

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