scholarly journals Eicosapentaenoic Acid Reduces Adiposity, Glucose Intolerance and Increases Oxygen Consumption Independently of Uncoupling Protein 1

2019 ◽  
Vol 63 (7) ◽  
pp. 1800821 ◽  
Author(s):  
Mandana Pahlavani ◽  
Latha Ramalingam ◽  
Emily K. Miller ◽  
Shane Scoggin ◽  
Kalhara R. Menikdiwela ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Eicosapentaenoic Acid ◽  
Glucose Intolerance ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1

scholarly journals The Role of Uncoupling Protein 1 in the Metabolism and Adiposity of RIIβ-Protein Kinase A-Deficient Mice

2004 ◽  
Vol 18 (9) ◽  
pp. 2302-2311 ◽  
Author(s):  
Michael A. Nolan ◽  
Maria A. Sikorski ◽  
G. Stanley McKnight
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Regulatory Subunit ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Kinase A

Abstract Mice lacking the RIIβ regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity. RIIβ−/− mice also have an increase in resting oxygen consumption along with a 4-fold increase in the brown adipose-specific mitochondrial uncoupling protein 1 (UCP1). In this study, we examined the basis for UCP1 induction and tested the hypothesis that the induced levels of UCP1 in RIIβ null mice are essential for the lean phenotype. The induction of UCP1 occurred at the protein but not the mRNA level and correlated with an increase in mitochondria in brown adipose tissue. Mice lacking both RIIβ and UCP1 (RIIβ−/−/Ucp1−/−) were created, and the key parameters of metabolism and body composition were studied. We discovered that RIIβ−/− mice exhibit nocturnal hyperactivity in addition to the increased oxygen consumption at rest. Disruption of UCP1 in RIIβ−/− mice reduced basal oxygen consumption but did not prevent the nocturnal hyperactivity. The double knockout animals also retained the lean phenotype of the RIIβ null mice, demonstrating that induction of UCP1 and increased resting oxygen consumption is not the cause of leanness in the RIIβ mutant mice.

Fish Oil Protects Wild Type and Uncoupling Protein 1‐Deficient Mice from Obesity and Glucose Intolerance by Increasing Energy Expenditure

2019 ◽  
Vol 63 (7) ◽  
pp. 1800813 ◽  
Author(s):  
Tiago E. Oliveira ◽  
Érique Castro ◽  
Thiago Belchior ◽  
Maynara L. Andrade ◽  
Adriano B. Chaves‐Filho ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Fish Oil ◽  
Glucose Intolerance ◽  
Uncoupling Protein ◽  
Wild Type ◽  
Uncoupling Protein 1 ◽  
Deficient Mice

scholarly journals A Change in Liver Metabolism but Not in Brown Adipose Tissue Thermogenesis Is an Early Event in Ovariectomy-Induced Obesity in Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 2881-2891 ◽  
Author(s):  
Mariana Nigro ◽  
Anderson T. Santos ◽  
Clarissa S. Barthem ◽  
Ruy A. N. Louzada ◽  
Rodrigo S. Fortunato ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Brown Adipose Tissue ◽  
Glucose Homeostasis ◽  
Uncoupling Protein ◽  
Tolerance Test ◽  
Uncoupling Protein 1 ◽  
Ovx Rats ◽  
Bat Mitochondria ◽  
Brown Adipose

Menopause is associated with increased visceral adiposity and disrupted glucose homeostasis, but the underlying molecular mechanisms related to these metabolic changes are still elusive. Brown adipose tissue (BAT) plays a key role in energy expenditure that may be regulated by sexual steroids, and alterations in glucose homeostasis could precede increased weight gain after ovariectomy. Thus, the aim of this work was to evaluate the metabolic pathways in both the BAT and the liver that may be disrupted early after ovariectomy. Ovariectomized (OVX) rats had increased food efficiency as early as 12 days after ovariectomy, which could not be explained by differences in feces content. Analysis of isolated BAT mitochondria function revealed no differences in citrate synthase activity, uncoupling protein 1 expression, oxygen consumption, ATP synthesis, or heat production in OVX rats. The addition of GDP and BSA to inhibit uncoupling protein 1 decreased oxygen consumption in BAT mitochondria equally in both groups. Liver analysis revealed increased triglyceride content accompanied by decreased levels of phosphorylated AMP-activated protein kinase and phosphorylated acetyl-CoA carboxylase in OVX animals. The elevated expression of gluconeogenic enzymes in OVX and OVX + estradiol rats was not associated with alterations in glucose tolerance test or in serum insulin but was coincident with higher glucose disposal during the pyruvate tolerance test. Although estradiol treatment prevented the ovariectomy-induced increase in body weight and hepatic triglyceride and cholesterol accumulation, it was not able to prevent increased gluconeogenesis. In conclusion, the disrupted liver glucose homeostasis after ovariectomy is neither caused by estradiol deficiency nor is related to increased body mass.

scholarly journals The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1

2020 ◽  
Vol 295 (17) ◽  
pp. 5588-5601
Author(s):  
Sho Sugawara ◽  
Yusuke Kanamaru ◽  
Shiori Sekine ◽  
Lila Maekawa ◽  
Akinori Takahashi ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Energy Consumption ◽  
Energy Expenditure ◽  
Phosphatase Activity ◽  
Protein Phosphatase ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
A Genome ◽  
Brown Adipose

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.

scholarly journals Glucose Intolerance in Aging Male IGFBP-3 Transgenic Mice: Differential Effects of Human IGFBP-3 and Its Mutant IGFBP-3 Devoid of IGF Binding Ability

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 462-474 ◽  
Author(s):  
K. Hoa Nguyen ◽  
Xing-Hai Yao ◽  
Adam G. Erickson ◽  
Suresh Mishra ◽  
B. L. Grégoire Nyomba
Keyword(s):  
Insulin Secretion ◽  
Glucose Intolerance ◽  
Uncoupling Protein ◽  
Lipid Homeostasis ◽  
Wild Type ◽  
Uncoupling Protein 1 ◽  
Β Cell ◽  
Binding Ability ◽  
Igf Binding ◽  
Igfbp 3

We have reported a reduction of insulin secretion and glucose intolerance in young mice overexpressing human IGFBP-3 (phosphoglycerate kinase [PGK]BP3) or its mutant Gly56/Gly80/Gly81-IGFBP-3 (PGKmutBP3) under the PGK promoter. Here, we investigated changes in glucose and lipid homeostasis with age in PGKBP3 and PGKmutBP3 mice compared with wild-type mice. Body weight, glucose tolerance, insulin tolerance, visceral fat, interscapular brown adipose tissue (BAT), serum lipids, and pancreas histology were examined at age 3, 6, and 12 months. Murine IGFBP-3 was similar in all mouse genotypes and decreased with age in parallel with total IGF-1. Visceral fat and BAT masses increased in PGKmutBP3 mice, but not in PGKBP3 mice. Glucose tolerance was impaired in both PGKBP3 and PGKmutBP3 mice. However, PGKBP3 mice had increased expression of uncoupling protein-1 in BAT and reduced adiposity, and continued to have smaller pancreatic β-cell mass and reduced insulin secretion through age 12 months. In contrast, PGKmutBP3 mice developed insulin resistance with age in association with pancreatic β-cell hyperplasia, impaired expression of uncoupling protein-1 in BAT, and increased adiposity. In addition, both PGKBP3 and PGKmutBP3 mice had elevated glycerol in the circulation, but only PGKBP3 mice had elevated free fatty acids and only PGKmutBP3 mice had elevated triglycerides. Estimated free IGF-1 did not increase with age in transgenic mice, as it did in wild-type mice. Thus, overexpression of human IGFBP-3 or its mutant devoid of IGF binding ability leads to glucose intolerance with, however, different effects on insulin secretion, insulin sensitivity, and lipid homeostasis in aging mice.

Evidence of Browning of White Adipocytes in Poorly Survived Fat Grafts in Patients

2021 ◽  
Author(s):  
Tong Liu ◽  
Su Fu ◽  
Qian Wang ◽  
Hao Cheng ◽  
Dali Mu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uncoupling Protein ◽  
Fold Increase ◽  
Fat Grafting ◽  
Electronic Microscopy ◽  
Uncoupling Protein 1 ◽  
Fat Transfer ◽  
Flap Transfer ◽  
Fat Grafts ◽  
White Adipocytes

Abstract Background Browning adipocytes induced by burn and cancer were assumed less viable and more prone to necrosis for their hypermetabolic properties. Recent studies have shown browning of white adipose after fat engraftment in mice. Objectives We tend to evaluate whether fat transfer could induce browning biogenesis in fat grafts in humans and if it is associated with graft necrosis. Methods Necrotic adipose grafts were excised from 11 patients diagnosed with fat necrosis after fat grafting or flap transfer. Non-necrotic fat grafts were from 5 patients undergoing revisionary surgeries after flap transfer. Histology and electronic microscopy, protein and gene expression of browning related marker analyses were performed. Results Fat grafts with necrosis demonstrated a higher gene expression level of uncoupling protein-1 (>5-fold increase, **p<0.01), a master beige adipocyte marker, than non-necrotic fat grafts. Electronic microscopy and histology showed that browning adipocytes were presented in necrotic adipose in patients. Conclusions Fat transfer induced browning adipocytes in patients and was evident in patients with post grafting necrosis.

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.

Growth factor regulation of uncoupling protein-1 mRNA expression in brown adipocytes

2002 ◽  
Vol 282 (1) ◽  
pp. C105-C112 ◽  
Author(s):  
Bibian García ◽  
Maria-Jesús Obregón
Keyword(s):  
Growth Factor ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Mrna Levels ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Proliferation And Differentiation ◽  
Epidermal Growth ◽  
Continuous Presence

To study the effect of the mitogens epidermal growth factor (EGF), acidic and basic fibroblast growth factors (aFGF and bFGF), and vasopressin on brown adipocyte differentiation, we analyzed the expression of uncoupling protein-1 (UCP-1) mRNA. Quiescent brown preadipocytes express high levels of UCP-1 mRNA in response to triiodothyronine (T3) and norepinephrine (NE). The addition of serum or the mitogenic condition aFGF + vasopressin + NE or EGF + vasopressin + NE decreases UCP-1 mRNA. A second addition of mitogens further decreases UCP-1 mRNA. Treatment with aFGF or bFGF alone increases UCP-1 mRNA, whereas the addition of EGF or vasopressin dramatically reduces UCP-1 mRNA levels. The continuous presence of T3 increases UCP-1 mRNA levels in cells treated with EGF, aFGF, or bFGF. The effect of T3 on the stimulation of DNA synthesis also was tested. T3 inhibits the mitogenic activity of aFGF and bFGF. In conclusion, mitogens like aFGF or bFGF allow brown adipocyte differentiation, whereas EGF and vasopressin inhibit the differentiation process. T3 behaves as an important hormone that regulates both brown adipocyte proliferation and differentiation.

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