scholarly journals Mitochondrial Biogenesis and Remodeling during Adipogenesis and in Response to the Insulin Sensitizer Rosiglitazone

2003 ◽  
Vol 23 (3) ◽  
pp. 1085-1094 ◽  
Author(s):  
Leanne Wilson-Fritch ◽  
Alison Burkart ◽  
Gregory Bell ◽  
Karen Mendelson ◽  
John Leszyk ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Gradient Centrifugation ◽  
Light And Electron Microscopy ◽  
Fold Increase ◽  
Mitochondrial Proteins ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Insulin Sensitizer ◽  
Adipose Differentiation ◽  
Whole Body Metabolism

ABSTRACT White adipose tissue is an important endocrine organ involved in the control of whole-body metabolism, insulin sensitivity, and food intake. To better understand these functions, 3T3-L1 cell differentiation was studied by using combined proteomic and genomic strategies. The proteomics approach developed here exploits velocity gradient centrifugation as an alternative to isoelectric focusing for protein separation in the first dimension. A 20- to 30-fold increase in the concentration of numerous mitochondrial proteins was observed during adipogenesis, as determined by mass spectrometry and database correlation analysis. Light and electron microscopy confirmed a large increase in the number of mitochondrion profiles with differentiation. Furthermore, mRNA profiles obtained by using Affymetrix GeneChips revealed statistically significant increases in the expression of many nucleus-encoded mitochondrial genes during adipogenesis. Qualitative changes in mitochondrial composition also occur during adipose differentiation, as exemplified by increases in expression of proteins involved in fatty acid metabolism and of mitochondrial chaperones. Furthermore, the insulin sensitizer rosiglitazone caused striking changes in mitochondrial shape and expression of selective mitochondrial proteins. Thus, although mitochondrial biogenesis has classically been associated with brown adipocyte differentiation and thermogenesis, our results reveal that mitochondrial biogenesis and remodeling are inherent to adipose differentiation per se and are influenced by the actions of insulin sensitizers.

Skeletal muscle mitochondrial uncoupling drives endocrine cross-talk through the induction of FGF21 as a myokine

2014 ◽  
Vol 306 (5) ◽  
pp. E469-E482 ◽  
Author(s):  
Susanne Keipert ◽  
Mario Ost ◽  
Kornelia Johann ◽  
Francine Imber ◽  
Martin Jastroch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Uncoupling Protein ◽  
Ectopic Expression ◽  
Metabolic Phenotype ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Fibroblast Growth Factor 21 ◽  
Mitochondrial Uncoupling ◽  
Whole Body Metabolism

UCP1-Tg mice with ectopic expression of uncoupling protein 1 (UCP1) in skeletal muscle (SM) are a model of improved substrate metabolism and increased longevity. Analysis of myokine expression showed an induction of fibroblast growth factor 21 (FGF21) in SM, resulting in approximately fivefold elevated circulating FGF21 in UCP1-Tg mice. Despite a reduced muscle mass, UCP1-Tg mice showed no evidence for a myopathy or muscle autophagy deficiency but an activation of integrated stress response (ISR; eIF2α/ATF4) in SM. Targeting mitochondrial function in vitro by treating C2C12 myoblasts with the uncoupler FCCP resulted in a dose-dependent activation of ISR, which was associated with increased expression of FGF21, which was also observed by treatment with respiratory chain inhibitors antimycin A and myxothiazol. The cofactor required for FGF21 action, β-klotho, was expressed in white adipose tissue (WAT) of UCP1-Tg mice, which showed an increased browning of WAT similar to what occurred in altered adipocyte morphology, increased brown adipocyte markers (UCP1, CIDEA), lipolysis (HSL phosphorylation), and respiratory capacity. Importantly, treatment of primary white adipocytes with serum of transgenic mice resulted in increased UCP1 expression. Additionally, UCP1-Tg mice showed reduced body length through the suppressed IGF-I-GH axis and decreased bone mass. We conclude that the induction of FGF21 as a myokine is coupled to disturbance of mitochondrial function and ISR activation in SM. FGF21 released from SM has endocrine effects leading to increased browning of WAT and can explain the healthy metabolic phenotype of UCP1-Tg mice. These results confirm muscle as an important endocrine regulator of whole body metabolism.

scholarly journals Prohibitin overexpression in adipocyte induces mitochondrial biogenesis, leads to obesity development and affects whole‐body metabolism in a gender specific manner (765.3)

2014 ◽  
Vol 28 (S1) ◽  
Author(s):  
Sudharsana Ande ◽  
K. Hoa Nguyen ◽  
G. Pauline Padilla‐Meier ◽  
Wahida Wahida ◽  
B.L. Grégoire Nyomba ◽  
...  
Keyword(s):  
Mitochondrial Biogenesis ◽  
Whole Body ◽  
Specific Manner ◽  
Whole Body Metabolism ◽  
Gender Specific

Adipokines as key players in β cell function and failure

2019 ◽  
Vol 133 (22) ◽  
pp. 2317-2327 ◽  
Author(s):  
Nicolás Gómez-Banoy ◽  
James C. Lo
Keyword(s):  
Metabolic Diseases ◽  
Cell Function ◽  
Whole Body ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
Cell Axis ◽  
Β Cell Function ◽  
Prevalence Of Obesity ◽  
Specific Factors ◽  
Whole Body Metabolism

Abstract The growing prevalence of obesity and its related metabolic diseases, mainly Type 2 diabetes (T2D), has increased the interest in adipose tissue (AT) and its role as a principal metabolic orchestrator. Two decades of research have now shown that ATs act as an endocrine organ, secreting soluble factors termed adipocytokines or adipokines. These adipokines play crucial roles in whole-body metabolism with different mechanisms of action largely dependent on the tissue or cell type they are acting on. The pancreatic β cell, a key regulator of glucose metabolism due to its ability to produce and secrete insulin, has been identified as a target for several adipokines. This review will focus on how adipokines affect pancreatic β cell function and their impact on pancreatic β cell survival in disease contexts such as diabetes. Initially, the “classic” adipokines will be discussed, followed by novel secreted adipocyte-specific factors that show therapeutic promise in regulating the adipose–pancreatic β cell axis.

scholarly journals PSIX-33 Docosahexaenoic Acid (DHA) but not Eicosapentaenoic Acid (EPA) induces the trans-differentiation of C2C12 into white-like adipocytes phenotype

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 309-310
Author(s):  
Yan Huang ◽  
Saeed Ghnaimawi ◽  
Yongjie Wang ◽  
Shilei Zhang ◽  
Jamie Baum
Keyword(s):  
Mitochondrial Biogenesis ◽  
Cultured Cells ◽  
Adipogenic Differentiation ◽  
The Body ◽  
C2c12 Cells ◽  
Brown Adipocyte ◽  
Marker Genes ◽  
Induction Medium ◽  
Spare Capacity ◽  
Epa And Dha

Abstract Muscle-derived stem cells (MDSCs, or myoblasts) play an important role in myotubes regeneration. However, these cells can differentiate into adipocytes once exposed to EPA and DHA, which are highly suggested during pregnancy. The objective of this study aims at determining the effect of isolated EPA and DHA on C2C12 cells undergoing white and brown adipogenic differentiation. Confluent cultured cells were treated with white and brown adipocyte induction medium (WIM and BIM respectively) with 50µM EPA and 50µM DHA separately. DHA treated groups differentiated into white-like adipocyte by down-regulating the expression of myogenic genes such as MyoD, MyoG, and Mrf4; but promoted white adipocyte marker genes(P < 0.05). Moreover, cells treated with WIM and DHA exhibited a decrease in mitochondrial biogenesis through suppressing PGC1a and TFAM expression (P < 0.05). Also, DHA promoted the expression of lipolysis regulating genes. DHA impaired C2C12 cells browning through reducing the mitochondrial biogenesis by significantly suppressing the expression of COX7a1, PGC1a, and UCP3 genes (P < 0.05). DHA treated groups showed an increased accumulation of lipid droplets and suppressed maximal mitochondrial respiration and spare capacity. EPA treatment reduced myogenesis regulating genes (P < 0.05) but did not affect adipogenic genes (P >0.05). Likewise, EPA suppressed the expression of WAT signature genes (P < 0.05), indicating its antagonism to DHA. EPA and WIM treatment suppressed the expression of TFAM and PGC1a, but did not affect PGC1a protein level. Although mitochondrial biogenic gene expression was reduced in EPA and BIDM treated group, no changes in mitochondrial function were observed. EPA supplementation did not affect the differential route of C2C12 into brown adipocytes. To conclude, EPA and DHA may similarly affect the integrity of muscle tissue, but DHA is a potent adipogenic and lipogenic factor that can change the metabolic profile of the body by increasing intramuscular fat.

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.

Isolation of blood and intracellular forms of Trypanosoma cruzi from rats and other rodents and preliminary studies of their metabolism

Parasitology ◽  
1978 ◽  
Vol 76 (2) ◽  
pp. 159-176 ◽  
Author(s):  
W. E. Gutteridge ◽  
B. Cover ◽  
Maria Gaborak
Keyword(s):  
Trypanosoma Cruzi ◽  
Blood Cells ◽  
Light And Electron Microscopy ◽  
Deae Cellulose ◽  
Whole Body ◽  
Differential Centrifugation ◽  
Γ Irradiation ◽  
Hind Limb Muscle ◽  
Radio Tracer

SummaryIsolation of blood and intracellular forms of Trypanosoma cruzi was made mainly from rats (90–110 g) which had received 580 rad of whole-body γ-irradiation not more than 24 h before subcutaneous inoculation with 107 trypomastigotes of the Sonya strain of T. cruzi. Unirradiated chinchillas (250–350 g) were, however, used for some experiments. Blood forms were isolated using a technique involving differential centrifugation to remove most of the erythrocytes and DEAE–cellulose chromatography to remove the remaining blood cells. Overall recoveries were usually in the range 30–70%. Parasites were mainly (approximately 98%) broad forms and were motile, metabolically active (as judged by respiratory and radio-tracer incorporation studies) and had lost none of their infectivity for mice. Intracellular forms were isolated from hind-limb muscle tissue. This was disrupted in an MSE tissue homogenizer and the homogenate incubated with DNase, collagenase and trypsin. Parasites, contaminated only by a few blood cells, were then obtained by differential centrifugation. For purer preparations, a terminal sucrose gradient step was used. Recoveries ranged between 40 and 70%. About 1–3% of the parasites isolated were epimastigotes and trypomastigotes; the remainder are probably best collectively termed ‘amastigotes’, though they were pointed and most had a short, free flagellum. They were undamaged as judged by light and electron microscopy and metabolically active as judged by respiratory and radio-tracer incorporation studies. However, the infectivity for mice of both these purified preparations and the initial cell homogenates could be accounted for by the epimastigotes and trypomastigotes present in them. Preliminary biochemical studies with isolated parasites have shown that blood, intracellular and culture forms of T. cruzi have a respiratory system which is in part sensitive to CN- and that all forms synthesize nucleic acids and proteins when incubated in vitro. There appears, however, to be a lack of DNA synthesis in blood stages, and thus it is not surprising that these forms do not divide.

Whole body metabolism is improved by hemin added to high fat diet while counteracted by nitrite: a mouse model of processed meat consumption.

2021 ◽  
Author(s):  
Diana Abu Halaka ◽  
Ofer Gover ◽  
Einat Rauchbach ◽  
Shira Zelber-Sagi ◽  
Betty Schwartz ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Food Industry ◽  
Food Additives ◽  
Whole Body ◽  
Processed Meat ◽  
Traditional Food ◽  
High Fat ◽  
Curing Agents ◽  
Whole Body Metabolism ◽  
Processed Meat Consumption

Nitrites and nitrates are traditional food additives used as curing agents in the food industry. They inhibit the growth of microorganisms and convey a typical pink color to the meat....

KCTD10 regulates brown adipose tissue thermogenesis and metabolic function via Notch Signaling

2021 ◽  
Author(s):  
Mingsheng Ye ◽  
Liping Luo ◽  
Qi Guo ◽  
Guanghua Lei ◽  
Chao Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Notch Signaling ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Notch Signaling Pathway ◽  
Whole Body ◽  
Brown Adipocyte ◽  
Metabolic Function ◽  
Brown Adipose

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 (PDIP1) family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 (UCP1) expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.

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