scholarly journals Co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins in the lactation-induced mitochondrial hypotrophy of rat brown fat

1995 ◽  
Vol 308 (3) ◽  
pp. 749-752 ◽  
Author(s):  
I Martin ◽  
M Giralt ◽  
O Viñas ◽  
R Iglesias ◽  
T Mampel ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Mitochondrial Genome ◽  
Cytochrome C Oxidase ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Relative Content ◽  
Nuclear Genes ◽  
Mitochondrial Proteins ◽  
Mrna Levels ◽  
Brown Adipose

The relative abundance of the mitochondrial-encoded mRNAs for cytochrome c oxidase subunit II and NADH dehydrogenase subunit I was lower in brown adipose tissue (BAT) from lactating rats than in virgin controls. This decrease was in parallel with a significant decrease in mitochondrial 16 S rRNA levels and in the relative content of mitochondrial DNA in the tissue. BAT from lactating rats showed lowered mRNA expression of the nuclear-encoded genes for the mitochondrial uncoupling protein, subunit IV of cytochrome c oxidase and the adenine nucleotide translocase isoforms ANT1 and ANT2, whereas mRNA levels for the ATP synthase beta-subunit were unchanged. However, the relative content of this last protein was lower in BAT mitochondria from lactating rats than in virgin controls. It is concluded that lactation-induced mitochondrial hypotrophy in BAT is associated with a co-ordinate decrease in the expression of the mitochondrial genome and nuclear genes for mitochondrial proteins. This decrease is caused by regulatory events acting at different levels, including pre- and post-transcriptional regulation. BAT appears to be a useful model with which to investigate the molecular mechanisms involved in the co-ordination of the expression of the mitochondrial and nuclear genomes during mitochondrial biogenesis.

scholarly journals Adaptative decrease in expression of the mRNA for uncoupling protein and subunit II of cytochrome c oxidase in rat brown adipose tissue during pregnancy and lactation

1989 ◽  
Vol 263 (3) ◽  
pp. 965-968 ◽  
Author(s):  
I Martin ◽  
M Giralt ◽  
O Viñas ◽  
R Iglesias ◽  
T Mampel ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Mrna Expression ◽  
Cytochrome C Oxidase ◽  
Uncoupling Protein ◽  
Late Pregnancy ◽  
Brown Fat ◽  
Breeding Cycle ◽  
Brown Adipose ◽  
Pregnancy And Lactation ◽  
Brown Fat Mitochondria

Uncoupling-protein (UCP) mRNA expression is decreased to 15% of virgin control levels between days 10 and 15 of pregnancy, and remains at these low values during late pregnancy and lactation. Abrupt weaning of mid-lactating rats causes a slight but significant increase in UCP mRNA. Expression of mRNA for subunit II of cytochrome c oxidase (COII) decreased to half that of virgin control in late pregnancy and during lactation. Whereas COII mRNA expression is in step with the known modifications of brown-fat mitochondria content during the breeding cycle of the rat, UCP mRNA expression appears to be diminished much earlier than the mitochondrial proton-conductance-pathway activity. On the other hand, the reactivity of brown fat to increase expression of UCP and COII mRNAs in response to acute cold or noradrenaline treatment is not impaired during lactation.

scholarly journals Sequential changes in the expression of mitochondrial protein mRNA during the development of brown adipose tissue in bovine and ovine species. Sudden occurrence of uncoupling protein mRNA during embryogenesis and its disappearance after birth

1989 ◽  
Vol 257 (3) ◽  
pp. 665-671 ◽  
Author(s):  
L Casteilla ◽  
O Champigny ◽  
F Bouillaud ◽  
J Robelin ◽  
D Ricquier
Keyword(s):  
Adipose Tissue ◽  
Cytochrome C ◽  
Brown Adipose Tissue ◽  
Cytochrome C Oxidase ◽  
Uncoupling Protein ◽  
Subcutaneous Tissue ◽  
Mitochondrial Protein ◽  
Sequence Of Events ◽  
Brown Adipose

Samples of adipose tissue were obtained from different sites in bovine and ovine foetuses and newborns. RNA was isolated and analysed using bovine cDNA and ovine genomic probe for uncoupling protein (UCP), cDNA for subunits III and IV of cytochrome c oxidase and cDNA for ADP/ATP carrier. UCP mRNA was characterized for the first time in foetal bovine and ovine adipose tissue. It appeared later than mRNA of cytochrome c oxidase subunit III, and increased dramatically at birth (10-fold). ADP/ATP carrier mRNA was expressed at a lower level but also increased 10-fold at birth. It was demonstrated that UCP mRNA reached its highest level at birth in all bovine adipose tissues studied, except subcutaneous tissue. It disappeared quickly afterwards, being no longer detectable two days after birth. Similar variations were observed in newborn lambs. ADP/ATP carrier mRNA showed the same pattern of expression as UCP mRNA; although it was still lightly expressed two days after birth, it disappeared soon afterwards. Only mRNAs for cytochrome c oxidase subunits III and IV remained at the same level during the first postnatal week. On the basis of these data and of observations reported in the literature a sequence of events for the development of brown adipose cells in vivo is proposed. Soon after birth the perirenal adipose tissue of ruminants, which still contains mitochondria of typical brown adipose tissue morphology and high levels of cytochrome c oxidase mRNA, lacks UCP mRNA. Can it still be considered as brown fat? Ruminant species appear to be attractive models to study both the differentiation of brown adipose tissue and its possible conversion to white fat in large animals.

Thermogenic activity and capacity of brown fat in fasted and refed golden hamsters

1987 ◽  
Vol 252 (5) ◽  
pp. R987-R993 ◽  
Author(s):  
I. Levin ◽  
P. Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Cytochrome C ◽  
Brown Adipose Tissue ◽  
Cytochrome C Oxidase ◽  
Golden Hamster ◽  
Oxidase Activity ◽  
Uncoupling Protein ◽  
Mitochondrial Mass ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis

The effects of different food deprivation regimens on the thermogenic activity and capacity of brown adipose tissue in the golden hamster have been investigated. Thermogenesis in the tissue was assessed by measurements of tissue cytochrome-c oxidase activity, mitochondrial GDP binding, and the specific mitochondrial concentration of uncoupling protein. The thermogenic activity and capacity of brown adipose tissue were found to be markedly reduced in fasted or underweight hamsters. Measurements of cytochrome-c oxidase activity indicate that the reductions were caused exclusively by a loss in mitochondrial mass, uncoupling protein concentration and GDP binding to mitochondria remaining unchanged. The decrease in brown adipose tissue thermogenesis was associated with a reduction in the capacity for nonshivering thermogenesis in the whole animal. Hamsters recovered from weight losses without increasing their food intake, and the recovery was accompanied by a normalization in mitochondrial mass in brown adipose tissue. Mitochondrial mass was, however, restored only after 10 days of ad libitum refeeding. These results suggest that the reduction in energy expenditure in the fasted hamster could relate to a decrease in brown adipose tissue thermogenesis, in addition to the previously reported decreases in resting metabolic rate and locomotor activity. Reductions in thermogenesis may also represent a further mechanism by which energy stores recover in the golden hamster without postfast hyperphagia.

scholarly journals Eicosapentaenoic Acid Increases Browning Markers in Subcutaneous Adipose Tissue and Primary Adipocytes from Wild Type and UCP-1 Deficient Mice (P15-007-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Shasika Jayarathne ◽  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Shane Scoggin ◽  
Naima Moustaid-Moussa
Keyword(s):  
Adipose Tissue ◽  
Eicosapentaenoic Acid ◽  
Subcutaneous Adipose Tissue ◽  
Uncoupling Protein ◽  
Fibroblast Growth Factor 21 ◽  
Chow Diet ◽  
Mrna Levels ◽  
Wild Type ◽  
Brown Adipose ◽  
Subcutaneous Adipose

Abstract Objectives Brown adipose tissue (BAT) regulates energy balance through thermogenesis, in part via uncoupling protein -1 (UCP-1). White adipose tissue (WAT), namely subcutaneous adipose tissue (SAT) can convert to a beige/brite adipose tissue phenotype (browning) under thermogenic conditions such as cold. We previously reported that eicosapentaenoic acid (EPA) reduced obesity and glucose intolerance, and increased UCP-1 in BAT of B6 mice at ambient temperature (22°C); and these effects were attenuated at thermoneutral environment (28–30°C). We hypothesized that EPA exerts anti-obesity effects on SAT, including increased browning, adipocyte hypotrophy; and these effects require UCP-1. Methods Six-week-old B6 wild type (WT) and UCP-1 knock-out (KO) male mice were maintained at thermoneutral environment and fed high fat diet (HF) with or without 36 g/kg of AlaskOmega EPA-enriched fish oil (800 mg/g) for 14 weeks; and SAT was collected for histological, gene and protein analyses. SAT was also prepared from chow diet-fed WT and KO mice at ambient environment to prepare stroma vascular cells, which were differentiated into adipocytes, treated with 100uM EPA for 48 hours then harvested for mRNA and protein analyses. Results KO mice fed HF diets had the highest body weight (P < 0.05) among all groups. EPA reduced fat cell size in both WT and KO mice fed the EPA diet. mRNA levels of fibroblast growth factor-21 (FGF-21) were higher in SAT of WT mice fed EPA compared to WT mice fed HF (P < 0.05), with no differences between the KO genotype. KO mice fed HF diets had lower levels of UCP-3 in SAT compared to WT mice fed HF (P < 0.05), which was rescued only in the KO mice fed EPA (P < 0.05). UCP-1 protein levels were very low in SAT tissues, and UCP-2 mRNA levels were similar across all groups in SAT. Interestingly, EPA significantly (P < 0.05) increased mRNA expression of UCP-2, UCP-3 and FGF21 in differentiated SAT adipocytes from both WT and KO compared to control. Furthermore, UCP-1 mRNA levels were significantly higher in WT adipocytes treated with EPA, compared to non-treated cells (P < 0.05). Additional mechanistic studies are currently underway to further dissect adipose depot differences in EPA effects in WT vs. KO mice. Conclusions Our data suggest that EPA increases SAT browning, independently of UCP-1. Funding Sources NIH/NCCIH.

Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise

2000 ◽  
Vol 279 (4) ◽  
pp. E806-E814 ◽  
Author(s):  
Henriette Pilegaard ◽  
George A. Ordway ◽  
Bengt Saltin ◽  
P. Darrell Neufer
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Uncoupling Protein ◽  
Pyruvate Dehydrogenase Kinase ◽  
Heme Oxygenase 1 ◽  
Metabolic Efficiency ◽  
Vastus Lateralis Muscle ◽  
Mrna Levels

Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60–90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to β-actin) increased by three- to sevenfold in response to exercise, peaking after 1–2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise ( n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.

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.

scholarly journals Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice

2018 ◽  
Vol 19 (10) ◽  
pp. 2904 ◽  
Author(s):  
Christian Carpéné ◽  
Saioa Gómez-Zorita ◽  
Alice Chaplin ◽  
Josep Mercader
Keyword(s):  
Adipose Tissue ◽  
Phosphoenolpyruvate Carboxykinase ◽  
De Novo ◽  
Uncoupling Protein ◽  
De Novo Lipogenesis ◽  
Metabolic Effects ◽  
Mrna Levels ◽  
Brown Adipose ◽  
High Sucrose ◽  
Sucrose Drinking

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.

Abstract 15546: Loss of Mitochondrial UCP3-Cytochrome c Oxidase Complexes Underlies Maladaptive Autophagy and Cardiac Failure in Anthracycline Cardiotoxicity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Rimpy Dhingra ◽  
Victoria Margulets ◽  
Davindar Jassal ◽  
Gerald Dorn ◽  
Lorrie A Kirshenbaum
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Cytochrome C Oxidase ◽  
Cardiac Failure ◽  
Uncoupling Protein ◽  
Mitochondrial Morphology ◽  
Necrotic Cell Death ◽  
Mitochondrial Targeting ◽  
Necrotic Cell ◽  
Anthracycline Cardiotoxicity

Doxorubicin is known for its cardiotoxic effects and inducing cardiac failure. Herein we demonstrate a novel signaling pathway that functionally links activation and preferential mitochondrial targeting of Bnip3 to doxorubicin cardiotoxicity. Perturbations to mitochondria including increased calcium, ROS, loss of αΨm and mPTP opening were observed in cardiac myocytes treated with doxorubicin. This coincided with a decline in maximal respiratory capacity, loss of respiratory chain complexes of uncoupling protein 3 (UCP3) and cytochrome c oxidase complex IV subunit 1, (COX) and cell viability. Impaired mitochondrial function was accompanied by an accumulated increase in autophagosomes and necrosis demonstrated by increase release of LDH, cTnT and loss of nuclear High Mobility Group Protein 1 (HMGB-1) immunoreactivity. Interestingly, pharmacological or genetic inhibition of autophagy with 3-methyl adenine (3-MA), or Atg7 knock-down suppressed necrotic cell death induced by doxorubicin. Conversely, loss of function of Bnip3 or mutations of Bnip3 defective for mitochondrial targeting restored UCP3-COX complexes, mitochondrial respiratory integrity and suppressed necrotic cell death induced by doxorubicin. Finally, mice germ-line deficient for Bnip3 were resistant to the cytotoxic effects of doxorubicin displaying mitochondrial morphology, cardiac function and survival rates comparable to vehicle treated control mice. To our knowledge the findings of the present study provide the first direct evidence that doxorubicin triggers maladaptive autophagy and necrotic cell death of ventricular myocytes by a mechanism mutually dependent and obligatorily linked to Bnip3. Hence, therapeutic interventions to selectively inhibit Bnip3 may prove beneficial in suppressing mitochondrial injury and heart failure in cancer patients undergoing doxorubicin treatment.

Abstract 015: Regulation of Resting Metabolism by the Angiotensin AT 2 Receptor

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Nicole K Littlejohn ◽  
Benjamin J Weidemann ◽  
Nicole A Pearson ◽  
Kathleen R Markan ◽  
Matthew J Potthoff ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Resting Metabolic Rate ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Interscapular Brown Adipose Tissue ◽  
Normal Number ◽  
Human Renin ◽  
Brown Adipose ◽  
Resting Metabolism

The renin-angiotensin system (RAS) positively correlates with obesity, and contributes to energy homeostasis through opposing actions in the brain and adipose. We hypothesize that site- and receptor-specific modulation may represent a novel therapeutic target for obesity. Transgenic “sRA” mice exhibit brain-specific RAS hyperactivity through expression of human renin in neurons (synapsin promoter) and human angiotensinogen via its own promoter. Previously we documented that sRA mice exhibit a suppressed circulating RAS, and an elevated resting metabolic rate (RMR) that is sensitive to replacement of circulating angiotensin II or the AT 2 receptor (AT 2 R) agonist, CGP-42112a (CGP, 100 ng/kg/min, s.c.). sRA mice consume more food than littermate controls (con n=7, 12.98±0.65 vs sRA n=8, 15.41±0.70 g/d, P<0.05), but because of a major suppression of digestive efficiency (con 77.6±2.3 vs sRA 59.3±4.7 % consumed, P<0.05), sRA mice absorb a normal number of calories (con 10.04±0.50 vs sRA 9.07±0.76 kcal/d). Chronic CGP had no effect on total daily caloric absorption (con+CGP n=7, 9.83±0.95 vs sRA+CGP n=5, 9.32±0.80 kcal/d); however CGP appears to disproportionately increase weight gain in sRA mice (vehicle +0.33±0.49 vs CGP +1.54±0.47 g/8 wks, P=0.27) compared to control mice (vehicle +2.12±1.00 vs CGP +2.47±0.73 g/8 wks, P=0.73), consistent with a suppression of energy expenditure by CGP. Given the increased RMR and core temperature in sRA mice, we next examined the expression of uncoupling protein-1 (UCP1) content of thermogenic adipose tissues by Western blot (all n=3, vs perilipin). Interscapular brown adipose tissue UCP1 was unchanged in sRA mice (94±6%), and weakly suppressed by CGP treatment (84±4% of sRA). Inguinal adipose UCP1 was increased in sRA mice (198±13%), and this was suppressed by CGP treatment (72±9% of sRA). UCP1 mRNA levels paralleled protein in both fat types. Cultured adipocytes from 4 day old AT 2 -deficient mice exhibited increased UCP1 protein vs littermate controls (190%). Further, CGP (10 nM) reduced UCP1 in control adipocytes (by 30%). These data support a suppressive action of AT 2 R upon RMR most likely through UCP1. Inguinal adipose AT 2 R may therefore contribute to obesity through suppression of RMR.

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