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 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 The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Romain Girard ◽  
Sarah Tremblay ◽  
Christophe Noll ◽  
Stéphanie St-Jean ◽  
Christine Jones ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
White Adipose Tissue ◽  
Whole Body ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Diet Induced Obesity ◽  
Regulatory Circuit ◽  
Body Energy

AbstractThe transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.

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 At the heart of mitochondrial quality control: many roads to the top

2021 ◽  
Author(s):  
Roberta A. Gottlieb ◽  
Honit Piplani ◽  
Jon Sin ◽  
Savannah Sawaged ◽  
Syed M. Hamid ◽  
...  
Keyword(s):  
Quality Control ◽  
Unfolded Protein Response ◽  
Mitochondrial Biogenesis ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Quality Control ◽  
Unfolded Protein ◽  
Selective Elimination ◽  
Protein Response ◽  
Mitochondrial Unfolded Protein Response

AbstractMitochondrial quality control depends upon selective elimination of damaged mitochondria, replacement by mitochondrial biogenesis, redistribution of mitochondrial components across the network by fusion, and segregation of damaged mitochondria by fission prior to mitophagy. In this review, we focus on mitochondrial dynamics (fusion/fission), mitophagy, and other mechanisms supporting mitochondrial quality control including maintenance of mtDNA and the mitochondrial unfolded protein response, particularly in the context of the heart.

scholarly journals Ursodeoxycholic Acid Regulates Hepatic Energy Homeostasis and White Adipose Tissue Macrophages Polarization in Leptin-Deficiency Obese Mice

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 253 ◽  
Author(s):  
Yu-Sheng Chen ◽  
Hsuan-Miao Liu ◽  
Tzung-Yan Lee
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Dysfunction ◽  
Ursodeoxycholic Acid ◽  
White Adipose Tissue ◽  
Whole Body ◽  
Bile Acid Metabolism ◽  
Obese Mice ◽  
Alcoholic Fatty Liver ◽  
Tissue Macrophage ◽  
Stat3 Phosphorylation

Obesity has been shown to play a role in the pathogenesis of several forms of metabolic syndrome, including non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. Ursodeoxycholic acid (UDCA) has been shown to possess antioxidant and anti-inflammatory properties and prevents mitochondrial dysfunction in the progression of obesity-associated diseases. The aim of the study was to evaluate the mechanisms of UDCA during obesity-linked hepatic mitochondrial dysfunction and obesity-associated adipose tissue macrophage-induced inflammation in obese mice. UDCA significantly decreased lipid droplets, reduced free fatty acids (FFA) and triglycerides (TG), improved mitochondrial function, and enhanced white adipose tissue browning in ob/ob mice. This is associated with increased hepatic energy expenditure, mitochondria biogenesis, and incorporation of bile acid metabolism (Abca1, Abcg1 mRNA and BSEP, FGFR4, and TGR5 protein). In addition, UDCA downregulated NF-κB and STAT3 phosphorylation by negative regulation of the expression of SOCS1 and SOCS3 signaling. These changes were accompanied by decreased angiogenesis, as shown by the downregulation of VEGF, VCAM, and TGF-βRII expression. Importantly, UDCA is equally effective in reducing whole body adiposity. This is associated with decreased adipose tissue expression of macrophage infiltration (CD11b, CD163, and CD206) and lipogenic capacity markers (lipofuscin, SREBP-1, and CD36). Furthermore, UDCA significantly upregulated adipose browning in association with upregulation of SIRT-1-PGC1-α signaling in epididymis adipose tissue (EWAT). These results suggest that multi-targeted therapies modulate glucose and lipid biosynthesis fluxes, inflammatory response, angiogenesis, and macrophage differentiation. Therefore, it may be suggested that UDCA treatment may be a novel therapeutic agent for obesity.

scholarly journals Tissue-specific expression of Sprouty1 in mice protects against high-fat diet-induced fat accumulation, bone loss and metabolic dysfunction

2011 ◽  
Vol 108 (6) ◽  
pp. 1025-1033 ◽  
Author(s):  
Sumithra Urs ◽  
Terry Henderson ◽  
Phuong Le ◽  
Clifford J. Rosen ◽  
Lucy Liaw
Keyword(s):  
Adipose Tissue ◽  
Bone Loss ◽  
Bone Mass ◽  
Body Fat ◽  
High Fat Diet ◽  
Conditional Knockout ◽  
Whole Body ◽  
High Fat ◽  
Tissue Specific ◽  
Diet Induced Obesity

We recently characterised Sprouty1 (Spry1), a growth factor signalling inhibitor as a regulator of marrow progenitor cells promoting osteoblast differentiation at the expense of adipocytes. Adipose tissue-specific Spry1 expression in mice resulted in increased bone mass and reduced body fat, while conditional knockout of Spry1 had the opposite effect with decreased bone mass and increased body fat. Because Spry1 suppresses normal fat development, we tested the hypothesis that Spry1 expression prevents high-fat diet-induced obesity, bone loss and associated lipid abnormalities, and demonstrate that Spry1 has a long-term protective effect on mice fed a high-energy diet. We studied diet-induced obesity in mice with fatty acid binding promoter-driven expression or conditional knockout of Spry1 in adipocytes. Phenotyping was performed by whole-body dual-energy X-ray absorptiometry, microCT, histology and blood analysis. In conditional Spry1-null mice, a high-fat diet increased body fat by 40 %, impaired glucose regulation and led to liver steatosis. However, overexpression of Spry1 led to 35 % (P < 0·05) lower body fat, reduced bone loss and normal metabolic function compared with single transgenics. This protective phenotype was associated with decreased circulating insulin (70 %) and leptin (54 %; P < 0·005) compared with controls on a high-fat diet. Additionally, Spry1 expression decreased adipose tissue inflammation by 45 %. We show that conditional Spry1 expression in adipose tissue protects against high-fat diet-induced obesity and associated bone loss.

scholarly journals Erythropoietin Signaling: A Novel Regulator of White Adipose Tissue Inflammation During Diet-Induced Obesity

Diabetes ◽  
2014 ◽  
Vol 63 (7) ◽  
pp. 2415-2431 ◽  
Author(s):  
M. Alnaeeli ◽  
B. M. Raaka ◽  
O. Gavrilova ◽  
R. Teng ◽  
T. Chanturiya ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Diet Induced Obesity
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