scholarly journals Exercise Rescues Gene Pathways Involved in Vascular Expansion and Promotes Functional Angiogenesis in Subcutaneous White Adipose Tissue

2019 ◽  
Vol 20 (8) ◽  
pp. 2046 ◽  
Author(s):  
So Yun Min ◽  
Heather Learnard ◽  
Shashi Kant ◽  
Olga Gealikman ◽  
Raziel Rojas-Rodriguez ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Whole Body ◽  
Vascular Density ◽  
Subcutaneous White Adipose Tissue ◽  
Whole Body Metabolism

Exercise mitigates chronic diseases such as diabetes, cardiovascular diseases, and obesity; however, the molecular mechanisms governing protection from these diseases are not completely understood. Here we demonstrate that exercise rescues metabolically compromised high fat diet (HFD) fed mice, and reprograms subcutaneous white adipose tissue (scWAT). Using transcriptomic profiling, scWAT was analyzed for HFD gene expression changes that were rescued by exercise. Gene networks involved in vascularization were identified as prominent targets of exercise, which led us to investigate the vasculature architecture and endothelial phenotype. Vascular density in scWAT was found to be compromised in HFD, and exercise rescued this defect. Similarly, angiogenic capacity as measured by ex vivo capillary sprouting was significantly promoted with exercise. Together, these data demonstrate that exercise enhances scWAT vascularization and functional capacity for angiogenesis, and can prevent the detrimental effects of HFD. The improvement in these indices correlates with improvement of whole-body metabolism, suggesting that scWAT vascularization may be a potential therapeutic target for metabolic disease.

scholarly journals Interactive effects of aging and aerobic capacity on energy metabolism–related metabolites of serum, skeletal muscle, and white adipose tissue

GeroScience ◽  
2021 ◽  
Author(s):  
Haihui Zhuang ◽  
Sira Karvinen ◽  
Timo Törmäkangas ◽  
Xiaobo Zhang ◽  
Xiaowei Ojanen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Amino Acid ◽  
White Adipose Tissue ◽  
Aerobic Capacity ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Disease Risk ◽  
Whole Body ◽  
Whole Body Metabolism

AbstractAerobic capacity is a strong predictor of longevity. With aging, aerobic capacity decreases concomitantly with changes in whole body metabolism leading to increased disease risk. To address the role of aerobic capacity, aging, and their interaction on metabolism, we utilized rat models selectively bred for low and high intrinsic aerobic capacity (LCRs/HCRs) and compared the metabolomics of serum, muscle, and white adipose tissue (WAT) at two time points: Young rats were sacrificed at 9 months of age, and old rats were sacrificed at 21 months of age. Targeted and semi-quantitative metabolomics analysis was performed on the ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS) platform. The effects of aerobic capacity, aging, and their interaction were studied via regression analysis. Our results showed that high aerobic capacity is associated with an accumulation of isovalerylcarnitine in muscle and serum at rest, which is likely due to more efficient leucine catabolism in muscle. With aging, several amino acids were downregulated in muscle, indicating more efficient amino acid metabolism, whereas in WAT less efficient amino acid metabolism and decreased mitochondrial β-oxidation were observed. Our results further revealed that high aerobic capacity and aging interactively affect lipid metabolism in muscle and WAT, possibly combating unfavorable aging-related changes in whole body metabolism. Our results highlight the significant role of WAT metabolism for healthy aging.

scholarly journals PO-043 The Effects of One-Time High Intensity Intermittent Training on Expression of LC3 Gene in Rats’ White Adipose Tissue

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Qishu Zhou ◽  
Chunyu Liang ◽  
Yafei Li ◽  
Yi Yan
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Intensity ◽  
High Fat Diet ◽  
Intermittent Exercise ◽  
Diet Group ◽  
Control Group ◽  
High Fat ◽  
Subcutaneous White Adipose Tissue ◽  
White Fat

Objective  To investigate the effect of one-time high-intensity intermittent exercise in white fat autophagy in obese rats and provide a theoretical basis of the molecular mechanism of exercise fat loss. Methods  Eighteen male 3-weeks-old rats were selected and divided into control group fed with normal diet (C), high-fat diet group fed with high fat diet (H). After 16 weeks, there were twelve obesity rats that divided into diet group (HS) and exercise group (HE). The other six control group rats of 19 weeks age were used as the standard (CS group). OE group did the high intensity intermittent exercise once. The CS group and the CS group were kept quietly. Three groups were taken subcutaneous white adipose tissue(S) and epididymal white adipose tissue (E) immediately after exercise. Mensurate the expression of LC3 gene in the tissue using the fluorescent quantitative PCR. Results 1. The expression of LC3 mRNA from white fat tissue was different to the tissues, which the expression of epididymal white adipose tissue of each group was higher than that in subcutaneous white adipose tissue (P <0.01). 2. Compared with CS group, the expression of epididymal white fat adipose tissue LC3 mRNA decreased (P<0.01) and the expression of the subcutaneous white adipose tissue increased from HS group (P <0.05). 3. Compared with OS group, the expression of epididymal white fat adipose tissue LC3 mRNA decreased (P<0.05) and the expression of subcutaneous white adipose tissue decreased from OS group. Conclusions The expression of LC3mRNA in epididymal white fat adipose tissue of rats was significantly higher than that of subcutaneous white fat. The changes of LC3mRNA expression of adipose tissue caused by high-fat diet have tissue differences. One-time high-intensity intermittent exercise can reduce the expression of LC3mRNA in fat tissue of obese rats. Its regulatory mechanism needs to be further studied.

scholarly journals Endothelial-specific FoxO1 depletion prevents obesity-related disorders by increasing vascular metabolism and growth

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Martina Rudnicki ◽  
Ghoncheh Abdifarkosh ◽  
Emmanuel Nwadozi ◽  
Sofhia V Ramos ◽  
Armin Makki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Tissue Expansion ◽  
Tissue Level ◽  
Whole Body ◽  
Vascular Density ◽  
High Fat ◽  
Fasting Glycemia ◽  
Underlying Mechanisms

Impaired angiogenesis is a hallmark of metabolically dysfunctional adipose tissue in obesity. However, the underlying mechanisms restricting angiogenesis within this context remain ill-defined. Here, we demonstrate that induced endothelial-specific depletion of the transcription factor Forkhead Box O1 (FoxO1) in male mice led to increased vascular density in adipose tissue. Upon high-fat diet feeding, endothelial cell FoxO1-deficient mice exhibited even greater vascular remodeling in the visceral adipose depot, which was paralleled with a healthier adipose tissue expansion, higher glucose tolerance and lower fasting glycemia concomitant with enhanced lactate levels. Mechanistically, FoxO1 depletion increased endothelial proliferative and glycolytic capacities by upregulating the expression of glycolytic markers, which may account for the improvements at the tissue level ultimately impacting whole-body glucose metabolism. Altogether, these findings reveal the pivotal role of FoxO1 in controlling endothelial metabolic and angiogenic adaptations in response to high-fat diet and a contribution of the endothelium to whole-body energy homeostasis.

scholarly journals Srebp-1c/Fgf21/Pgc-1α Axis Regulated by Leptin Signaling in Adipocytes—Possible Mechanism of Caloric Restriction-Associated Metabolic Remodeling of White Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2054
Author(s):  
Masaki Kobayashi ◽  
Seira Uta ◽  
Minami Otsubo ◽  
Yusuke Deguchi ◽  
Ryoma Tagawa ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Caloric Restriction ◽  
White Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Fibroblast Growth Factor 21 ◽  
Leptin Signaling ◽  
Age Related ◽  
Metabolic Remodeling

Caloric restriction (CR) improves whole body metabolism, suppresses age-related pathophysiology, and extends lifespan in rodents. Metabolic remodeling, including fatty acid (FA) biosynthesis and mitochondrial biogenesis, in white adipose tissue (WAT) plays an important role in the beneficial effects of CR. We have proposed that CR-induced mitochondrial biogenesis in WAT is mediated by peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), which is transcriptionally regulated by sterol regulatory element-binding protein 1c (SREBP-1c), a master regulator of FA biosynthesis. We have also proposed that the CR-associated upregulation of SREBP-1 and PGC-1α might result from the attenuation of leptin signaling and the upregulation of fibroblast growth factor 21 (FGF21) in WAT. However, the detailed molecular mechanisms remain unclear. Here, we interrogate the regulatory mechanisms involving leptin signaling, SREBP-1c, FGF21, and PGC-1α using Srebp-1c knockout (KO) mice, mouse embryonic fibroblasts, and 3T3-L1 adipocytes, by altering the expression of SREBP-1c or FGF21. We show that a reduction in leptin signaling induces the expression of proteins involved in FA biosynthesis and mitochondrial biogenesis via SREBP-1c in adipocytes. The upregulation of SREBP-1c activates PGC-1α transcription via FGF21, but it is unlikely that the FGF21-associated upregulation of PGC-1α expression is a predominant contributor to mitochondrial biogenesis in adipocytes.

scholarly journals Mitochondrial Unfolded Protein Responses in White Adipose Tissue: Lipoatrophy, Whole-Body Metabolism and Lifespan

2021 ◽  
Vol 22 (6) ◽  
pp. 2854
Author(s):  
Masaki Kobayashi ◽  
Yuichiro Nezu ◽  
Ryoma Tagawa ◽  
Yoshikazu Higami
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Whole Body ◽  
Unfolded Protein ◽  
Diet Induced Obesity ◽  
Expression Of Genes ◽  
Whole Body Metabolism ◽  
Living Organisms ◽  
Protein Response ◽  
Mitochondrial Unfolded Protein Response

The mitochondrial unfolded protein response (UPRmt) is a stress response mediated by the expression of genes such as chaperones, proteases, and mitokines to maintain mitochondrial proteostasis. Certain genetically modified mice, which defect mitochondrial proteins specifically in adipocytes, developed atrophy of the white adipose tissue, resisted diet-induced obesity, and had altered whole-body metabolism. UPRmt, which has beneficial functions for living organisms, is termed “mitohormesis”, but its specific characteristics and detailed regulatory mechanism have not been elucidated to date. In this review, we discuss the function of UPRmt in adipose atrophy (lipoatrophy), whole-body metabolism, and lifespan based on the concept of mitohormesis.

scholarly journals Lyophilized Maqui (Aristotelia chilensis) Berry Induces Browning in the Subcutaneous White Adipose Tissue and Ameliorates the Insulin Resistance in High Fat Diet-Induced Obese Mice

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 360 ◽  
Author(s):  
Viviana Sandoval ◽  
Antoni Femenias ◽  
Úrsula Martínez-Garza ◽  
Hèctor Sanz-Lamora ◽  
Juan Castagnini ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Binding Protein ◽  
Fibroblast Growth Factor 21 ◽  
Obese Mice ◽  
High Fat ◽  
Subcutaneous White Adipose Tissue ◽  
Aristotelia Chilensis

Maqui (Aristotelia Chilensis) berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT). These changes correlated with an increased expression of the carbohydrate response element binding protein b (Chrebpb), the sterol regulatory binding protein 1c (Srebp1c) and Cellular repressor of adenovirus early region 1A–stimulated genes 1 (Creg1) and an improvement in the fibroblast growth factor 21 (FGF21) signaling. Our evidence suggests that maqui dietary supplementation activates the induction of fuel storage and thermogenesis characteristic of a brown-like phenotype in scWAT and counteracts the unhealthy metabolic impact of an HFD. This induction constitutes a putative strategy to prevent/treat diet-induced obesity and its associated comorbidities.

scholarly journals Tofogliflozin Improves Insulin Resistance in Skeletal Muscle and Accelerates Lipolysis in Adipose Tissue in Male Mice

Endocrinology ◽  
2015 ◽  
Vol 157 (3) ◽  
pp. 1029-1042 ◽  
Author(s):  
Atsushi Obata ◽  
Naoto Kubota ◽  
Tetsuya Kubota ◽  
Masahiko Iwamoto ◽  
Hiroyuki Sato ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Uptake ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
The Body ◽  
High Fat ◽  
Ad Libitum

Abstract Sodium glucose cotransporter 2 inhibitors have attracted attention as they exert antidiabetic and antiobesity effects. In this study, we investigated the effects of tofogliflozin on glucose homeostasis and its metabolic consequences and clarified the underlying molecular mechanisms. C57BL/6 mice were fed normal chow containing tofogliflozin (0.005%) for 20 weeks or a high-fat diet containing tofogliflozin (0.005%) for 8 weeks ad libitum. In addition, the animals were pair-fed in relation to controls to exclude the influence of increased food intake. Tofogliflozin reduced the body weight gain, mainly because of fat mass reduction associated with a diminished adipocyte size. Glucose tolerance and insulin sensitivity were ameliorated. The serum levels of nonesterified fatty acid and ketone bodies were increased and the respiratory quotient was decreased in the tofogliflozin-treated mice, suggesting the acceleration of lipolysis in the white adipose tissue and hepatic β-oxidation. In fact, the phosphorylation of hormone-sensitive lipase and the adipose triglyceride lipase protein levels in the white adipose tissue as well as the gene expressions related to β-oxidation, such as Cpt1α in the liver, were significantly increased. The hepatic triglyceride contents and the expression levels of lipogenic genes were decreased. Pair-fed mice exhibited almost the same results as mice fed an high-fat diet ad libitum. Moreover, a hyperinsulinemic-euglycemic clamp revealed that tofogliflozin improved insulin resistance by increasing glucose uptake, especially in the skeletal muscle, in pair-fed mice. Taken together, these results suggest tofogliflozin ameliorates insulin resistance and obesity by increasing glucose uptake in skeletal muscle and lipolysis in adipose tissue.

scholarly journals Metabolic remodeling of white adipose tissue in obesity

2014 ◽  
Vol 307 (3) ◽  
pp. E262-E277 ◽  
Author(s):  
Timothy D. Cummins ◽  
Candice R. Holden ◽  
Brian E. Sansbury ◽  
Andrew A. Gibb ◽  
Jasmit Shah ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Citrate Synthase ◽  
Krebs Cycle ◽  
Mitochondrial Respiratory Chain ◽  
Whole Body ◽  
Ultrastructural Changes ◽  
High Fat ◽  
Metabolic Remodeling

Adipose tissue metabolism is a critical regulator of adiposity and whole body energy expenditure; however, metabolic changes that occur in white adipose tissue (WAT) with obesity remain unclear. The purpose of this study was to understand the metabolic and bioenergetic changes occurring in WAT with obesity. Wild-type (C57BL/6J) mice fed a high-fat diet (HFD) showed significant increases in whole body adiposity, had significantly lower V̇o2, V̇co2, and respiratory exchange ratios, and demonstrated worsened glucose and insulin tolerance compared with low-fat-fed mice. Metabolomic analysis of WAT showed marked changes in lipid, amino acid, carbohydrate, nucleotide, and energy metabolism. Tissue levels of succinate and malate were elevated, and metabolites that could enter the Krebs cycle via anaplerosis were mostly diminished in high-fat-fed mice, suggesting altered mitochondrial metabolism. Despite no change in basal oxygen consumption or mitochondrial DNA abundance, citrate synthase activity was decreased by more than 50%, and responses to FCCP were increased in WAT from mice fed a high-fat diet. Moreover, Pgc1a was downregulated and Cox7a1 upregulated after 6 wk of HFD. After 12 wk of high-fat diet, the abundance of several proteins in the mitochondrial respiratory chain or matrix was diminished. These changes were accompanied by increased Parkin and Pink1, decreased p62 and LC3-I, and ultrastructural changes suggestive of autophagy and mitochondrial remodeling. These studies demonstrate coordinated restructuring of metabolism and autophagy that could contribute to the hypertrophy and whitening of adipose tissue in obesity.

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