Reduction of dietary obesity in aP2-Ucp transgenic mice: physiology and adipose tissue distribution

1996 ◽  
Vol 270 (5) ◽  
pp. E768-E775 ◽  
Author(s):  
J. Kopecky ◽  
Z. Hodny ◽  
M. Rossmeisl ◽  
I. Syrovy ◽  
L. P. Kozak
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Gene Promoter ◽  
Lipid Binding ◽  
Brown Fat ◽  
Mitochondrial Uncoupling ◽  
Dietary Obesity

We seek to determine whether increased energy dissipation in adipose tissue can prevent obesity. Transgenic mice with C57BL6/J background and the adipocyte lipid-binding protein (aP2) gene promoter directing expression of the mitochondrial uncoupling protein (UCP) gene in white and brown fat were used. Physiologically, UCP is essential for nonshivering thermogenesis in brown fat. Mice were assigned to a chow or a high-fat (HF) diet at 3 mo of age. Over the next 25 wk, gains of body weight were similar in corresponding subgroups (n = 6-8) of female and male mice: 4-5 g in chow nontransgenic and transgenic, 20 g in HF nontransgenic, and 9-11 g in HF transgenic mice. The lower body weight gain in the HF transgenic vs. nontransgenic mice corresponded to a twofold lower feed efficiency. Gonadal fat was enlarged, but subcutaneous white fat was decreased in the transgenic vs. nontransgenic mice in both dietary conditions. The results suggest that UCP synthesized from the aP2 gene promoter is capable of reducing dietary obesity.

scholarly journals Brown fat is essential for cold-induced thermogenesis but not for obesity resistance in aP2-Ucp mice

1998 ◽  
Vol 274 (3) ◽  
pp. E527-E533 ◽  
Author(s):  
Bohumír Stefl ◽  
Alena Janovská ◽  
Zdenek Hodný ◽  
Martin Rossmeisl ◽  
Milada Horáková ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transgenic Mice ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Transgenic Animals ◽  
Brown Fat ◽  
Mitochondrial Uncoupling ◽  
Brown Adipose ◽  
Total Energy Balance

The role of brown adipose tissue in total energy balance and cold-induced thermogenesis was studied. Mice expressing mitochondrial uncoupling protein 1 (UCP-1) from the fat-specific aP2 gene promoter (heterozygous and homozygous aP2 -Ucp transgenic mice) and their nontransgenic C57BL6/J littermates were used. The transgenic animals are resistant to obesity induced by a high-fat diet, presumably due to ectopic synthesis of UCP-1 in white fat. These animals exhibited atrophy of brown adipose tissue, as indicated by smaller size of brown fat and reduction of its total UCP-1 and DNA contents. Norepinephrine-induced respiration (measured in pentobarbital sodium-anesthetized animals) was decreased proportionally to the dosage of the transgene, and the homozygous (but not heterozygous) transgenic mice exhibited a reduction in their capacity to maintain body temperature in the cold. Our results indicate that the role of brown fat in cold-induced thermogenesis cannot be substituted by increased energy expenditure in other tissues.

scholarly journals Effect on Body Weight and Adipose Tissue by Cariprazine: A Head-to-Head Comparison Study to Olanzapine and Aripiprazole in Rats

2020 ◽  
Vol 88 (4) ◽  
pp. 50
Author(s):  
László-István Bába ◽  
Zsolt Gáll ◽  
Melinda Kolcsár ◽  
Zsuzsánna Pap ◽  
Zoltán V. Varga ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Partial Agonist ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Regulatory Element ◽  
Receptor Subtypes ◽  
Limited Information ◽  
Pharmacodynamic Profile

Cariprazine (Car) is a recently approved second generation antipsychotic (SGA) with unique pharmacodynamic profile, being a partial agonist at both dopamine D2/3 receptor subtypes, with almost 10 times greater affinity towards D3. SGAs are known to increase body weight, alter serum lipids, and stimulate adipogenesis but so far, limited information about the adverse effects is available with this drug. In order to study this new SGA with such a unique mechanism of action, we compared Car to substances that are considered references and are well characterized: olanzapine (Ola) and aripiprazole (Ari). We studied the effects on body weight and also assessed the adipogenesis in rats. The drugs were self-administered in two different doses to female, adult, Wistar rats for six weeks. Weekly body weight change, vacuole size of adipocytes, Sterol Regulatory Element Binding Protein-1 (SREBP-1) and Uncoupling Protein-1 (UCP-1) expression were measured from the visceral adipose tissue (AT). The adipocyte’s vacuole size, and UCP-1 expression were increased while body weight gain was diminished by Car. by increasing UCP-1 might stimulate the thermogenesis, that could potentially explain the weight gain lowering effect through enhanced lipolysis.

scholarly journals Dietary curcumin supplement promotes browning and energy expenditure in postnatal overfed rats

2020 ◽  
Author(s):  
Xiaolei Zhu ◽  
Susu Du ◽  
Qinhui Yan ◽  
Cuiting Min ◽  
Nan Zhou ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Blood Lipid ◽  
Standard Diet ◽  
Mrna Levels ◽  
Lower Body Weight ◽  
Normal Feeding

Abstract Background: Early postnatal overfeeding could result in metabolic imprinting that decreases energy expenditure following with white adipose tissue (WAT) gain throughout life. This research was to investigate whether curcumin (CUR) supplement could promote WAT browning and activate thermogenesis in postnatal overfed rats.Methods and results: This study adjusted the size of litters to three (small litters, SL) or ten (normal litters, NL) to mimic early postnatal overfeeding or normal feeding from postnatal day 3. From postnatal week 3 (weaning period), the SL rats were fed with a standard diet (SL) or a diet supplemented with 1% (SL1% CUR) or 2% (SL2% CUR) CUR for ten weeks. At postnatal week 13, SL rats with 1% or 2% CUR supplement had lower body weight and less WAT gain, had increased lean mass ratio, and their glucose tolerance and blood lipid levels had recovered to normal when compared to SL rats that did not receive the supplement. Moreover, increased respiratory exchange ratio (RER) and heat generation were consistent with expression levels of uncoupling protein 1 (UCP1) and other browning-related genes in the subcutaneous adipose tissue (SAT) of the SL2% CUR rats but not of the SL1% CUR rats. In addition, 2% CUR dietary supplement enhanced the serum norepinephrine (NE) levels in SL rats, with the upregulated mRNA levels of β3-adrenergic receptor (β3-AR) in SAT.Conclusion: Dietary CUR supplement attenuates body weight gain and metabolic disorders in SL, which might be induced by promoting browning of SAT and energy expenditure. Moreover, the benefits were more obvious in SL with 2% CUR supplement.

scholarly journals Dietary Supplementation with Dunaliella Tertiolecta Prevents Whitening of Brown Fat and Controls Diet-Induced Obesity at Thermoneutrality in Mice

Nutrients ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1686
Author(s):  
Yukari Yamashita ◽  
Tamaki Takeuchi ◽  
Yuki Endo ◽  
Ayumi Goto ◽  
Setsuko Sakaki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Dunaliella Tertiolecta ◽  
Brown Fat ◽  
Fibroblast Growth Factor 21 ◽  
High Group ◽  
Diet Induced Obesity ◽  
Brown Adipose

We investigated the effect of evodiamine-containing microalga Dunaliella tertiolecta (DT) on the prevention of diet-induced obesity in a thermoneutral C57BL/6J male (30 °C). It attenuates the activity of brown adipose tissue (BAT), which accelerates diet-induced obesity. Nine-week-old mice were fed a high-fat diet supplemented with 10 g (Low group) or 25 g (High group) DT powder per kg food for 12 weeks. Compared to control mice without DT supplementation, body weight gain was significantly reduced in the High group with no difference in food intake. Tissue analyses indicated maintenance of multilocular morphology in BAT and reduced fat deposition in liver in DT-supplemented mice. Molecular analysis showed a significant decrease in mammalian target of rapamycin−ribosomal S6 protein kinase signaling pathway in white adipose tissue and upregulation in mRNA expression of brown fat-associated genes including fibroblast growth factor-21 (Fgf21) and uncoupling protein 1 (Ucp1) in BAT in the High group compared to the control. In the experiments using C3H10T1/2 adipocytes, DT extract upregulated mRNA expression of brown fat-associated genes in dose-dependent and time-dependent manners, accompanied by a significant increase in secreted FGF21 levels. Our data show the ability of DT as a nutraceutical to prevent brown fat attenuation and diet-induced obesity in vivo.

scholarly journals The mitochondrial uncoupling protein gene in brown fat: correlation between DNase I hypersensitivity and expression in transgenic mice.

1991 ◽  
Vol 11 (8) ◽  
pp. 4147-4156 ◽  
Author(s):  
B B Boyer ◽  
L P Kozak
Keyword(s):  
Transgenic Mice ◽  
Protein Gene ◽  
Uncoupling Protein ◽  
Dnase I ◽  
Brown Fat ◽  
Hypersensitive Site ◽  
Mitochondrial Uncoupling ◽  
Mitochondrial Uncoupling Protein ◽  
Dnase I Hypersensitive Site ◽  
Uncoupling Protein Gene

The mitochondrial uncoupling protein gene is rapidly induced in mouse brown fat following cold exposure. To identify cis-regulatory elements, approximately 50 kb of chromatin surrounding the uncoupling protein gene was examined for its hypersensitivity to DNase I. Seven DNase I-hypersensitive sites were identified in the 5'-flanking DNA, and one site was identified in the 3'-flanking DNA. Transgenic mice with an uncoupling protein minigene were generated by microinjection of fertilized eggs with a transgene containing 3 kb of 5'-flanking DNA and 0.3 kb of 3'-flanking DNA. Expression of the transgene is restricted to brown fat and is cold inducible. Four additional transgenic lines were generated with a second transgene containing a 1.8-kb deletion in the 5'-flanking DNA, and expression of this minigene is absent in all tissues analyzed. A DNase I-hypersensitive site located in the 1.8-kb deletion contains a cyclic AMP response element that binds a brown fat tumor enriched nuclear factor. On the basis of these observations, we propose that a cis-acting regulatory sequence between -3 and -1.2 kb of the 5'-flanking region, possibly at a DNase I-hypersensitive site, is required for controlling uncoupling protein expression in vivo.

Postnatal development of uncoupling protein, uncoupling protein mRNA, and GLUT4 in adipose tissues of goats

1993 ◽  
Vol 265 (3) ◽  
pp. R676-R682 ◽  
Author(s):  
P. Trayhurn ◽  
M. E. Thomas ◽  
J. S. Keith
Keyword(s):  
Adipose Tissue ◽  
Glucose Transporter ◽  
Uncoupling Protein ◽  
Subcutaneous Fat ◽  
Brown Fat ◽  
Postnatal Life ◽  
Mitochondrial Uncoupling ◽  
Adipose Tissues ◽  
Perirenal Adipose Tissue ◽  
Fat Depots

Adipose tissues have been characterized in newborn goats on the basis of the presence of the 32,000-M(r) mitochondrial uncoupling protein (UCP) diagnostic of brown fat, and early postnatal developmental changes have been determined. Both internal (perirenal, pericardial, and omental) and subcutaneous (hindlimb and neck regions) adipose tissues in newborn goats contained UCP and are therefore brown fat. The insulin-sensitive glucose transporter, GLUT4, was also present in adipose tissues of newborn goats, implying a potential for insulin-stimulated glucose uptake at birth. UCP was still evident in the perirenal fat of goats at 3 wk of age, but the mitochondrial concentration was only 4%, and the amount per cell a mere 0.2%, of that in the newborn. UCP was not detectable, however, in either the omental or subcutaneous adipose tissue at 3 wk of age and had disappeared from the subcutaneous fat before 2 wk. In contrast to UCP, GLUT4 remained throughout the initial 3 wk of postnatal life. The mRNA for UCP was detected in perirenal adipose tissue of newborn goats, indicating that the gene coding for the protein is being expressed at around birth. UCP mRNA was not, however, detectable in the other fat depots; nor was it evident in the perirenal adipose tissue at > or = 2.5 days of age. It is concluded that the adipose tissues of newborn goats (both internal and subcutaneous) represent brown fat and that there is a rapid transition toward white fat over the first weeks of life. This transition occurs at different rates in different depots but is not markedly faster in goats than in other ruminants.(ABSTRACT TRUNCATED AT 250 WORDS)

Brown fat-specific mitochondrial uncoupling protein in adipose tissues of newborn reindeer

1991 ◽  
Vol 260 (6) ◽  
pp. R1229-R1234 ◽  
Author(s):  
P. Soppela ◽  
M. Nieminen ◽  
S. Saarela ◽  
J. S. Keith ◽  
J. N. Morrison ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Brown Fat ◽  
Mitochondrial Uncoupling ◽  
Molecular Weight Characteristic ◽  
Adipose Tissues ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose ◽  
Adverse Weather

Reindeer inhabit a severe arctic or subarctic environment, with the young born in early spring under adverse weather conditions. The extreme northern climate imposes a major thermal challenge to the newborn, and in the present study we have examined fetal, neonatal, and young (from 2 wk before birth to 16 mo postpartum) semidomesticated reindeer from northern Finland for the presence of thermogenic brown adipose tissue. Adipose tissues were removed, mitochondria were prepared, and the proteins were separated by molecular weight and blotted onto nitrocellulose membranes. The membranes were then probed for the presence of the 32,000-relative molecular weight mitochondrial uncoupling protein (UCP) unique to brown fat by use of a rabbit anti-(ground squirrel UCP) serum. Immunoreactivity at the molecular weight characteristic of UCP was present in perirenal, abdominal, inter(pre)scapular, sternal, intralumbar, vertebral, tracheal, inguinal, and omental-mesenteral adipose tissues of newborn reindeer (0-2 days of age). No immunoreactivity was detected in coronary adipose tissue. UCP was found at high levels in interscapular and perirenal adipose tissues of fetal reindeer at 2 wk before birth. Although the protein was present during the first few days postpartum, little immunoreactivity was found at 1 mo of age, and none was evident by 2 mo. UCP and its mRNA were also apparent in perirenal adipose tissue of the newborn of another species of Cervidae, the red deer. It is concluded, on the basis of the immunologic identification of UCP, that most adipose tissues of newborn reindeer represent functional brown fat but that there is a subsequent conversion to white adipose tissue by the 2nd mo of life.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals D-Mannitol Induces a Brown Fat-like Phenotype via a β3-Adrenergic Receptor-Dependent Mechanism

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 768
Author(s):  
Hui-Jeon Jeon ◽  
Dong Kyu Choi ◽  
JaeHeon Choi ◽  
Seul Lee ◽  
Heejin Lee ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Protein Kinase ◽  
White Adipose Tissue ◽  
Adrenergic Receptor ◽  
Uncoupling Protein ◽  
The Body ◽  
Brown Fat ◽  
White Adipocytes

The presence of brown adipocytes within white adipose tissue is associated with phenotypes that exhibit improved metabolism and proper body weight maintenance. Therefore, a variety of dietary agents that facilitate the browning of white adipocytes have been investigated. In this study, we screened a natural product library comprising 133 compounds with the potential to promote the browning of white adipocytes, and found that D-mannitol induces the browning of 3T3-L1 adipocytes by enhancing the expression of brown fat-specific genes and proteins, and upregulating lipid metabolism markers. D-mannitol also increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase 1 (ACC), suggesting a possible role in lipolysis and fat oxidation. Moreover, an increase in the expression of genes associated with D-mannitol-induced browning was strongly correlated with the activation of the β3-adrenergic receptor as well as AMPK, protein kinase A (PKA), and PPARγ coactivator 1α (PGC1α). D-mannitol effectively reduced the body weight of mice fed a high-fat diet, and increased the expression of β1-oxidation and energy expenditure markers, such as Cidea, carnitine palmityl transferase 1 (CPT1), uncoupling protein 1 (UCP1), PGC1α, and acyl-coenzyme A oxidase (ACOX1) in the inguinal white adipose tissue. Our findings suggest that D-mannitol plays a dual regulatory role by inducing the generation of a brown fat-like phenotype and enhancing lipid metabolism. These results indicate that D-mannitol can function as an anti-obesity supplement.

scholarly journals Cranberry Polyphenolic Extract Exhibits an Antiobesity Effect on High-Fat Diet–Fed Mice through Increased Thermogenesis

2020 ◽  
Vol 150 (8) ◽  
pp. 2131-2138 ◽  
Author(s):  
Fang Zhou ◽  
Jielong Guo ◽  
Xue Han ◽  
Yunxiao Gao ◽  
Qimin Chen ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
The Body ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Polyphenolic Extract ◽  
Brown Adipose

ABSTRACT Background Although polyphenol-rich cranberry extracts reportedly have an antiobesity effect, the exact reason for this remains unclear. Objectives In light of the reported health benefits of the polyphenolic compounds in cranberry, we investigated the effects and mechanism of a cranberry polyphenolic extract (CPE) in high-fat diet (HFD)–fed obese mice. Methods The distributions of individual CPE compounds were characterized by HPLC fingerprinting. Male C57BL/6J mice (4 wk old) were fed for 16 wk normal diet (ND, 10% fat energy) or HFD (60% fat energy) with or without 0.75% CPE in drinking water (HFD + CPE). Body and adipose depot weights, indices of glucose metabolism, energy expenditure (EE), and expression of genes related to brown adipose tissue (BAT) thermogenesis, and inguinal/epididymal white adipose tissue (iWAT/eWAT) browning were measured. Results After 16 wk, the body weight was 22.5% lower in the CPE-treated mice than in the HFD group but remained 17.9% higher than in the ND group. CPE treatment significantly increased EE compared with that of the ND and HFD groups. The elevated EE was linked with BAT thermogenesis, and iWAT/eWAT browning, shown by the induction of thermogenic genes, especially uncoupling protein 1 (Ucp1), and browning-related genes, including Cd137, a member of the tumor necrosis factor receptor superfamily (Tnfrsf9). The mRNA expression and abundance of uncoupling protein 1 in BAT of CPE-fed mice were 5.78 and 1.47 times higher than in the HFD group, and 0.61 and 1.12 times higher than in the ND group, respectively. Cd137 gene expression in iWAT and eWAT of CPE-fed mice were 2.35 and 3.13 times higher than in the HFD group, and 0.84 and 1.39 times higher than in the ND group, respectively. Conclusions Dietary CPE reduced but did not normalize HFD-induced body weight gain in male C57BL/6J mice, possibly by affecting energy metabolism.

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