scholarly journals Chronic Blockade of Nitric Oxide Synthesis Reduces Adiposity and Improves Insulin Resistance in High Fat-Induced Obese Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (10) ◽  
pp. 4548-4556 ◽  
Author(s):  
Kyoichiro Tsuchiya ◽  
Haruna Sakai ◽  
Noriko Suzuki ◽  
Fumiko Iwashima ◽  
Takanobu Yoshimoto ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Serine Phosphorylation ◽  
Mrna Levels ◽  
Obese Mice ◽  
High Fat ◽  
Brown Adipose

Genetic deletion of inducible nitric oxide synthase (NOS) in mice has been shown to improve high-fat diet (HFD)-induced insulin resistance. However, a pathophysiological role of endogenous nitric oxide (NO) in obesity-related insulin resistance remains controversial. To address this issue, we examined the metabolic phenotypes in HFD-induced obese mice with chronic blockade of NO synthesis by a NOS inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME). Six-week-old male C57BL/6j mice were provided free access to either a standard diet (SD) or a HFD and tap water with or without L-NAME (100 mg/kg·d) for 12 wk. L-NAME treatment significantly attenuated body weight gain of mice fed either SD or HFD without affecting calorie intake. L-NAME treatment in HFD-fed mice improved glucose tolerance and insulin sensitivity. HFD feeding induced inducible NOS mRNA expression, but not the other two NOS isoforms, in white adipose tissue (WAT) and skeletal muscle. L-NAME treatment up-regulated uncoupling protein-1 in brown adipose tissue of HFD-fed mice but down-regulated monocyte chemoattractant protein-1 and CD68 mRNAs levels in WAT. HFD feeding up-regulated leptin mRNA levels but conversely down-regulated adiponectin mRNA levels in WAT, but these effects were unaffected by L-NAME treatment. Moreover, L-NAME treatment also increased peroxisome proliferator-uncoupling protein-3 mRNA levels in skeletal muscles of HFD-fed mice. Increased urinary excretion of norepinephrine after HFD feeding was augmented in L-NAME-treated mice. Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 and serine phosphorylation of Akt/Akt2 in soleus muscle was markedly impaired in HFD-fed mice but reversed by L-NAME treatment. In conclusion, chronic NOS blockade by L-NAME in mice ameliorates HFD-induced adiposity and glucose intolerance, accompanied by reduced adipose inflammation and improved insulin signaling in skeletal muscle, suggesting that endogenous NO plays a modulatory role in the development of obesity-related insulin resistance.

Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia

2005 ◽  
Vol 288 (3) ◽  
pp. E625-E632 ◽  
Author(s):  
Jennifer H. Lee ◽  
John W. Bullen ◽  
Violeta L. Stoyneva ◽  
Christos S. Mantzoros
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
Mouse Models ◽  
Uncoupling Protein ◽  
High Fat ◽  
Resistant Mouse ◽  
Brown Adipose ◽  
Tnf Α ◽  
Resistin Mrna

Resistin is an adipocyte-secreted hormone proposed to link obesity with insulin resistance and diabetes, but no previous study has performed a joint quantitative evaluation of white adipose tissue (WAT) resistin mRNA expression and serum levels in relation to insulinemia and glycemia in mice. We have thus comparatively assessed WAT resistin mRNA expression and serum resistin levels in lean C57BL/6J mice and various mouse models of obesity, including diet-induced obese (DIO) C57BL/6J mice, high fat-fed TNF-α−/− mice, and brown adipose tissue (BAT)-deficient uncoupling protein-diphtheria toxin A chain (UCP1-DTA) mice. We also studied whether treatment with the weight-reducing and insulin-sensitizing compounds, MTII, an α-melanocyte-stimulating hormone analog, or CNTFAx15, a ciliary neurotrophic factor analog, alters resistin mRNA expression and/or circulating levels in lean and DIO C57BL/6J mice. We find that resistin mRNA expression is similar in DIO and lean C57BL/6J mice, as well as in TNF-α−/− and wild-type (WT) mice. Circulating resistin levels, however, are higher in DIO C57BL/6J, high fat-fed TNF-α−/−, and UCP1-DTA mice compared with lean controls. Moreover, although resistin mRNA expression is upregulated by MTII treatment for 24 h and downregulated by CNTFAx15 treatment for 3 or 7 days, circulating resistin levels are not altered by MTII or CNTFAx15 treatment. In addition, serum resistin levels, but not resistin mRNA expression levels, are correlated with body weight, and neither resistin mRNA expression nor serum resistin levels are correlated with serum insulin or glucose levels. We conclude that transcriptional regulation of resistin in WAT does not correlate with circulating resistin levels and that circulating resistin is unlikely to play a major endocrine role in insulin resistance or glycemia in mice.

Differential regulation of uncoupling protein gene homologues in multiple tissues of hibernating ground squirrels

1998 ◽  
Vol 275 (4) ◽  
pp. R1232-R1238 ◽  
Author(s):  
Bert B. Boyer ◽  
Brian M. Barnes ◽  
Bradford B. Lowell ◽  
Danica Grujic
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Ground Squirrels ◽  
Mrna Levels ◽  
Parallel Mechanisms ◽  
Mitochondrial Uncoupling ◽  
Spermophilus Parryii ◽  
Mitochondrial Uncoupling Protein ◽  
Brown Adipose

Nonshivering thermogenesis in brown adipose tissue (BAT) provides heat through activation of a mitochondrial uncoupling protein (UCP1), which causes futile electron transport cycles without the production of ATP. Recent discovery of two molecular homologues, UCP2, expressed in multiple tissues, and UCP3, expressed in muscle, has resulted in investigation of their roles in thermoregulatory physiology and energy balance. To determine the expression pattern of Ucp homologues in hibernating mammals, we compared relative mRNA levels of Ucp1, -2, and -3 in BAT, white adipose tissue (WAT), and skeletal muscle of arctic ground squirrels ( Spermophilus parryii) hibernating at different ambient and body temperatures, with levels determined in tissues from ground squirrels not in hibernation. Here we report significant increases in mRNA levels for Ucp2 in WAT (1.6-fold) and Ucp3 in skeletal muscle (3-fold) during hibernation. These results indicate the potential for a role of UCP2 and UCP3 in thermal homeostasis during hibernation and indicate that parallel mechanisms and multiple tissues could be important for nonshivering thermoregulation in mammals.

scholarly journals The Crude Extract fromPuerariaeFlower Exerts Antiobesity and Antifatty Liver Effects in High-Fat Diet-Induced Obese Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Tomoyasu Kamiya ◽  
Mayu Sameshima-Kamiya ◽  
Rika Nagamine ◽  
Masahito Tsubata ◽  
Motoya Ikeguchi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Uncoupling Protein ◽  
Expression Profiles ◽  
Folk Medicine ◽  
Hormone Sensitive Lipase ◽  
Leguminous Plant ◽  
Obese Mice ◽  
High Fat ◽  
Brown Adipose

Kudzu, a leguminous plant, has long been used in folk medicine. In particular, its flowers are used in Japanese and Chinese folk medicine for treating hangovers. We focused on the flower of Kudzu (Puerariae thomsonii), and we previously reported the antiobesity effect ofPuerariae thomsoniiflower extract (PFE) in humans. In this study, we conducted an animal study to investigate the effect of PFE on visceral fat and hepatic lipid levels in mice with diet-induced obesity. In addition, we focused on gene expression profiles to investigate the antiobesity mechanism of PFE. Male C57BL/6J mice were fed a high-fat diet (HFD) or an HFD supplemented with 5% PFE for 14 days. PFE supplementation significantly reduced body weight and white adipose tissue (WAT) weight. Moreover, in the histological analysis, PFE supplementation improved fatty liver. Hepatic reverse transcription-polymerase chain reaction revealed that PFE supplementation downregulated acetyl-CoA carboxylase expression. For adipose tissue, the expressions of hormone-sensitive lipase in WAT and uncoupling protein 1 in brown adipose tissue (BAT) were significantly upregulated. These results suggest that PFE exerts antiobesity and antifatty liver effects in high-fat diet-induced obese mice through suppressing lipogenesis in the liver, stimulating lipolysis in WAT, and promoting thermogenesis in BAT.

scholarly journals Adipose tissue uncoupling protein 1 levels and function are increased in a mouse model of developmental obesity induced by maternal exposure to high-fat diet

2018 ◽  
Vol 9 (4) ◽  
pp. 401-408 ◽  
Author(s):  
E. Bytautiene Prewit ◽  
C. Porter ◽  
M. La Rosa ◽  
N. Bhattarai ◽  
H. Yin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Respiration ◽  
Maternal Obesity ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
High Fat ◽  
Uncoupling Protein 1 ◽  
Protein Levels ◽  
Brown Adipose ◽  
And Function

AbstractWith brown adipose tissue (BAT) becoming a possible therapeutic target to counteract obesity, the prenatal environment could represent a critical window to modify BAT function and browning of white AT. We investigated if levels of uncoupling protein 1 (UCP1) and UCP1-mediated thermogenesis are altered in offspring exposed to prenatal obesity. Female CD-1 mice were fed a high-fat (HF) or standard-fat (SF) diet for 3 months before breeding. After weaning, all pups were placed on SF. UCP1 mRNA and protein levels were quantified using quantitative real-time PCR and Western blot analysis, respectively, in brown (BAT), subcutaneous (SAT) and visceral (VAT) adipose tissues at 6 months of age. Total and UCP1-dependent mitochondrial respiration were determined by high-resolution respirometry. A Student’st-test and Mann–Whitney test were used (significance:P<0.05). UCP1 mRNA levels were not different between the HF and SF offspring. UCP1 protein levels, total mitochondrial respiration and UCP1-dependent respiration were significantly higher in BAT from HF males (P=0.02,P=0.04,P=0.005, respectively) and females (P=0.01,P=0.04,P=0.02, respectively). In SAT, the UCP1 protein was significantly lower in HF females (P=0.03), and the UCP1-dependent thermogenesis was significantly lower from HF males (P=0.04). In VAT, UCP1 protein levels and UCP1-dependent respiration were significantly lower only in HF females (P=0.03,P=0.04, respectively). There were no differences in total respiration in SAT and VAT. Prenatal exposure to maternal obesity leads to significant increases in UCP1 levels and function in BAT in offspring with little impact on UCP1 levels and function in SAT and VAT.

scholarly journals Changes in insulin-receptor mRNA levels in skeletal muscle and brown adipose tissue of weanling rats during fasting and refeeding

1992 ◽  
Vol 68 (3) ◽  
pp. 583-592 ◽  
Author(s):  
Rachel M. Knott ◽  
Paul Trayhurn ◽  
John E. Hesketh
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Insulin Receptor ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Brown Adipose ◽  
Fasting And Refeeding

Tissue-specific alterations in insulin sensitivity occur in response to fasting and refeeding, as part of the integrated adaptive mechanisms employed to adjust to major changes in nutritional status. In the present study the effects of fasting and refeeding on insulin-receptor, actin and myosin mRNA levels in skeletal muscle, and insulin-receptor and uncoupling-protein mRNA in brown adipose tissue of rats have been examined. Insulin-receptor mRNA levels increased markedly in both skeletal muscle and brown adipose tissue after a 40 h fast, the increase being greater in brown fat (8-fold) than in muscle (2-fold). On refeeding for 4 h, the insulin-receptor mRNA level in both tissues declined rapidly to control levels. An increase in insulin-receptor mRNA level was also observed in brown adipose tissue after a 16 h fast, although not in skeletal muscle. In contrast to the insulin-receptor mRNA, the level of the mRNA for the mitochondrial uncoupling protein declined markedly in brown adipose tissue during a 40 h fast. These results indicate that insulin-receptor mRNA levels are modulated in response to the alterations in nutritional status that occur during fasting and refeeding; this may reflect a nutritional influence on transcription of the receptor-protein gene

scholarly journals Supplemental epilactose prevents metabolic disorders through uncoupling protein-1 induction in the skeletal muscle of mice fed high-fat diets

2015 ◽  
Vol 114 (11) ◽  
pp. 1774-1783 ◽  
Author(s):  
Yuki Murakami ◽  
Teruyo Ojima-Kato ◽  
Wataru Saburi ◽  
Haruhide Mori ◽  
Hirokazu Matsui ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Propionic Acid ◽  
Metabolic Disorders ◽  
Uncoupling Protein ◽  
C2c12 Cells ◽  
High Fat ◽  
Brown Adipose

AbstractObesity is one of the major health problems throughout the world. The present study investigated the preventive effect of epilactose – a rare non-digestible disaccharide – on obesity and metabolic disorders in mice fed high-fat (HF) diets. Feeding with HF diets increased body weight gain, fat pad weight and adipocyte size in mice (P<0·01), and these increases were effectively prevented by the use of supplemental epilactose without influencing food intake (P<0·01). Caecal pools of SCFA such as acetic and propionic acids in mice fed epilactose were higher compared with mice not receiving epilactose. Supplemental epilactose increased the expression of uncoupling protein (UCP)-1, which enhances energy expenditure, to 2-fold in the gastrocnemius muscle (P=0·04) and to 1·3-fold in the brown adipose tissue (P=0·02) in mice fed HF diets. Feeding HF diets induced pro-inflammatory macrophage infiltration into white adipose tissue, as indicated by the increased expression of monocyte chemotactic protein-1, TNF-α and F4/80, and these increases were attenuated by supplemental epilactose. In differentiated myogenic-like C2C12 cells, propionic acid, but not acetic or n-butyric acids, directly enhanced UCP-1 expression by approximately 2-fold (P<0·01). Taken together, these findings indicate that the epilactose-mediated increase in UCP-1 in the skeletal muscle and brown adipose tissue can enhance whole-body energy expenditure, leading to effective prevention of obesity and metabolic disorders in mice fed HF diets. It is suggested that propionic acid – a bacterial metabolite – acts as a mediator to induce UCP-1 expression in skeletal muscles.

Effect of high-fat diet, surrounding temperature, and enterostatin on uncoupling protein gene expression

2000 ◽  
Vol 279 (2) ◽  
pp. E293-E300 ◽  
Author(s):  
Catarina Rippe ◽  
Karin Berger ◽  
Charlotta Böiers ◽  
Daniel Ricquier ◽  
Charlotte Erlanson-Albertsson
Keyword(s):  
Adipose Tissue ◽  
Uncoupling Protein ◽  
Mrna Levels ◽  
High Fat ◽  
Ambient Temperatures ◽  
Long Term Effect ◽  
Brown Adipose ◽  
Fat Feeding ◽  
Ucp2 Mrna

Nonshivering thermogenesis induced in brown adipose tissue (BAT) during high-fat feeding is mediated through uncoupling protein 1 (UCP1). UCP2 is a recently identified homologue found in many tissues. To determine the role of UCP1 and UCP2 in thermoregulation and energy balance, we investigated the long-term effect of high-fat feeding on mRNA levels in mice at two different ambient temperatures. We also treated mice with the anorectic peptide enterostatin and compared mRNA levels in BAT, white adipose tissue (WAT), stomach, and duodenum. Here, we report that high-fat feeding at 23°C increased UCP1 and UCP2 levels in BAT four- and threefold, respectively, and increased UCP2 levels fourfold in WAT. However, at 29°C, UCP1 decreased, whereas UCP2 remained unchanged in BAT and increased twofold in WAT. Enterostatin increased UCP1 and decreased UCP2 mRNA in BAT. In stomach and duodenum, high-fat feeding decreased UCP2 mRNA, whereas enterostatin increased it. Our results suggest that the regulation of uncoupling protein mRNA levels by high-fat feeding is dependent on ambient temperature and that enterostatin is able to modulate it.

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.

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.

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