scholarly journals Altered Metabolism and Lipodystrophy in the Early B-Cell Factor 1-Deficient Mouse

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1611-1621 ◽  
Author(s):  
Jackie A. Fretz ◽  
Tracy Nelson ◽  
Yougen Xi ◽  
Douglas J. Adams ◽  
Clifford J. Rosen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
B Cell ◽  
White Adipose Tissue ◽  
Serum Glucose ◽  
The Body ◽  
Metabolic Phenotype ◽  
Wild Type ◽  
Glucose Levels ◽  
Marrow Adiposity ◽  
Early B Cell Factor

We previously reported that mice deficient for the transcription factor early B-cell factor (Ebf1) exhibit markedly increased numbers of osteoblasts, bone formation rate, and serum osteocalcin, but the bone marrow of Ebf1−/− mice is also striking in its increased marrow adiposity. The purpose of this work was to analyze the metabolic phenotype that accompanies the altered bone morphology of Ebf1−/− mice. Whereas marrow adiposity was increased, deposition of white adipose tissue in other regions of the body was severely reduced (sc 40–50%, abdominally 80–85%). Brown adipose exhibited decreased lipid deposition. Subcutaneous and perigonadal white adipose tissue showed a decrease in mRNA transcripts for peroxisomal proliferator-activated receptor-γ2 and CCAAT/enhancer-binding protein-β in Ebf1−/− tissue compared with wild type. Circulating levels of leptin were decreased in Ebf1−/− animals compared with their littermate controls (down 65-95%), whereas adiponectin remained comparable after 2 wk of age. Serum analysis also found the Ebf1−/− animals were hypoglycemic and hypotriglyceridemic. After ip injection of insulin, the serum glucose levels in Ebf1−/− mice took longer to recover, and after a glucose challenge the Ebf1−/− animals reached serum glucose levels almost twice that of their wild-type counterparts. Measurement of circulating pancreatic hormones revealed normal or reduced insulin levels in the Ebf1−/− mice, whereas glucagon was significantly increased (up 1.7- to 8.5-fold). Metabolically the Ebf1−/− mice had increased O2 consumption, CO2 production, food and water intake, and activity. Markers for gluconeogenesis, however, were decreased in the Ebf1−/− mice compared with controls. In conclusion, the Ebf1-deficient animals exhibit defects in adipose tissue deposition with increased marrow adiposity and impaired glucose mobilization.

scholarly journals Growth Hormone Receptor Antagonist Transgenic Mice Are Protected From Hyperinsulinemia and Glucose Intolerance Despite Obesity When Placed on a HF Diet

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 555-564 ◽  
Author(s):  
Tianxu Yang ◽  
Lara A. Householder ◽  
Ellen R. Lubbers ◽  
Edward O. List ◽  
Katie Troike ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Glucose Metabolism ◽  
Receptor Antagonist ◽  
White Adipose Tissue ◽  
Growth Hormone Receptor ◽  
Metabolic Stress ◽  
Tissue Expansion ◽  
Serum Glucose ◽  
Glucose Levels

Reduced GH levels have been associated with improved glucose metabolism and increased longevity despite obesity in multiple mouse lines. However, one mouse line, the GH receptor antagonist (GHA) transgenic mouse, defies this trend because it has reduced GH action and increased adiposity, but glucose metabolism and life span are similar to controls. Slight differences in glucose metabolism and adiposity profiles can become exaggerated on a high-fat (HF) diet. Thus, in this study, male and female GHA and wild-type (WT) mice in a C57BL/6 background were placed on HF and low-fat (LF) diets for 11 weeks, starting at 10 weeks of age, to assess how GHA mice respond to additional metabolic stress of HF feeding. On a HF diet, all mice showed significant weight gain, although GHA gained weight more dramatically than WT mice, with males gaining more than females. Most of this weight gain was due to an increase in fat mass with WT mice increasing primarily in the white adipose tissue perigonadal depots, whereas GHA mice gained in both the sc and perigonadal white adipose tissue regions. Notably, GHA mice were somewhat protected from detrimental glucose metabolism changes on a HF diet because they had only modest increases in serum glucose levels, remained glucose tolerant, and did not develop hyperinsulinemia. Sex differences were observed in many measures with males reacting more dramatically to both a reduction in GH action and HF diet. In conclusion, our findings show that GHA mice, which are already obese, are susceptible to further adipose tissue expansion with HF feeding while remaining resilient to alterations in glucose homeostasis.

scholarly journals SUN-590 27-Hydroxycholesterol Triggers the Whitening of Brown Adipose Tissue

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Arvand Asghari ◽  
Linh Bui ◽  
Robert Stephen ◽  
Michihisa Umetani
Keyword(s):  
Estrogen Receptor ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
Vehicle Control ◽  
The Body ◽  
Wild Type ◽  
Brown Adipose

Abstract 27-Hydroxycholesterol (27HC) is the most abundant oxysterol in circulation and metabolized by a P450 enzyme CYP7B1. Its levels closely correspond to those of cholesterol in the body. In addition, previously it was found that 27HC is an endogenous selective estrogen receptor modulator (SERM), which links cholesterol metabolism to estrogen receptor actions (1). Brown adipose tissue (BAT) is the primary source of energy expenditure and energy homeostasis, as well as body temperature maintenance. While previously it was believed that BAT activity is limited to neonates and young children, it is now recognized that BAT is also active in adult humans and its function is impaired by metabolic diseases such as obesity. BAT is also a secretory organ and produces brown adipokines, although the exact function of BAT and adipokines from this tissue in obesity has not been completely understood. Recently, it was reported that 27HC plays an important role in obesity and augments body weight gain in response to a high fat, high cholesterol (HFHC) diet by increasing pre-adipocyte population in the white adipose tissue. 27HC mimics the effects by HFHC diet-feeding on white adipose tissue, such as promoting the inflammation and macrophage infiltration (2). In this study, we explored the effect of 27HC on BAT morphology and function. First, we compared the morphology of BAT from wild-type mice and Cyp7b1-/- mice that have elevated levels of 27HC using H&E staining. Interestingly, brown adipocytes from Cyp7b1-/- mice were larger in cell size than those from wild-type mice, and the cells were mostly unilocular compared to the multilocular cells from wild-type mice, indicating the transition toward a “whitening” phenotype. Next, We treated mice fed a normal chow or a HFHC diet with 27HC or vehicle control for 8 weeks to examine the direct effect by 27HC on BAT. Similar to the phenotype in Cyp7b1-/-mice, 27HC increased the “whitening” of BAT regardless of the diet. We also determined the gene expression of brown adipocyte markers such as UCP1, PGC1a, and DIO2, and found that 27HC significantly decreased the expression of the BAT markers regardless of the diet, confirming the “whitening” observed in the morphology. Moreover, the energy expenditure in mice treated with 27HC was decreased compared to the vehicle control on a HFHC diet, suggesting that 27HC also alters BAT function. These results show that 27HC causes the whitening of BAT, and shed light on the important role of 27HC in brown adipose tissue function. Future experiments will be warranted toward further understanding of the role of 27HC in BAT function. Reference:(1) Umetani, Michihisa, et al. Nature medicine 13.10 (2007): 1185. (2) Asghari, Arvand, et al. Endocrinology 160.10 (2019): 2485-2494.

scholarly journals Early B Cell Factor 1 Regulates Adipocyte Morphology and Lipolysis in White Adipose Tissue

2014 ◽  
Vol 19 (6) ◽  
pp. 981-992 ◽  
Author(s):  
Hui Gao ◽  
Niklas Mejhert ◽  
Jackie A. Fretz ◽  
Erik Arner ◽  
Silvia Lorente-Cebrián ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
B Cell ◽  
White Adipose Tissue ◽  
Early B Cell Factor

White Adipose Tissue Depots in GHR−/− Mice: Age-Related Changes in Comparison to Wild-Type Controls

2011 ◽  
pp. P2-351-P2-351
Author(s):  
Lucila Sackmann Sala ◽  
Clare B Vesel ◽  
Ellen R Lubbers ◽  
Rachel D Munn ◽  
Katie M Troike ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Wild Type ◽  
Adipose Tissue Depots ◽  
Age Related ◽  
Age Related Changes

Abstract 1125: Mulberry Leaf Ameliorates The Production Of Adipocytokines By Inhibiting Oxidative Stress In White Adipose Tissue In db/db Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Masayuki Sugimoto ◽  
Hidenori Arai ◽  
Yukinori Tamura ◽  
Toshinori Murayama ◽  
Koh Ono ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Metabolic Disorders ◽  
The Body ◽  
Mulberry Leaf ◽  
The Metabolic Syndrome ◽  
Pparγ Agonist ◽  
Tnf Α

Mulberry leaf (ML) is commonly used to feed silkworms. Previous study showed that ML ameliorates atherosclerosis. However, its mechanism is not completely understood. Because dysregulated production of adipocytokines is involved in the development of the metabolic syndrome and cardiovascular disease, we examined the effect of ML on the production of adipocytokines and metabolic disorders related to the metabolic syndrome, and compared its effect with that of a PPARγ agonist, pioglitazone (Pio). By treating obese diabetic db/db mice with ML, Pio, and their combination, we investigated the mechanism by which they improve metabolic disorders. In this study, db/+m (lean control) and db/db mice were fed a standard diet with or without 3% (w/w) ML and/or 0.01% (w/w) Pio for 12 weeks from 9 weeks of age. At the end of the experiment we found that ML decreased plasma glucose and triglyceride by 32% and 30%, respectively. Interestingly, administration of ML in addition to Pio showed additive effects; further 40% and 30% reduction in glucose and triglyceride compared with Pio treatment, respectively. Moreover, administration of ML in addition to Pio suppressed the body weight increase by Pio treatment and reduced visceral/subcutaneous fat ratio by 20% compared with control db/db mice. Importantly, ML treatment increased expression of adiponectin in white adipose tissue (WAT) by 40%, which was only found in db/db mice, not in control db/+m mice. Combination of ML and Pio increased plasma adiponectin concentrations by 25% and its expression in WAT by 17% compared with Pio alone. In contrast, ML decreased expression of TNF-α and MCP-1 by 25% and 20%, respectively, and the addition of Pio resulted in a further decrease of these cytokines by about 45%. To study the mechanism, we examined the role of oxidative stress. ML decreased the amount of lipid peroxides by 43% and the expression of NADPH oxidase subunits in WAT, which was consistent with the results of TNF-α and MCP-1. Thus our results indicate that ML ameliorates adipocytokine dysregulation by inhibiting oxidative stress in WAT of obese mice, and that ML may have a potential for the treatment of the metabolic syndrome as well as reducing adverse effects of Pio.

Seasonal changes in hormone-sensitive and lipoprotein lipase mRNA concentrations in marmot white adipose tissue

1992 ◽  
Vol 262 (2) ◽  
pp. R177-R181 ◽  
Author(s):  
B. E. Wilson ◽  
S. Deeb ◽  
G. L. Florant
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
White Adipose Tissue ◽  
Mass Gain ◽  
The Body ◽  
Hormone Sensitive Lipase ◽  
Marmota Flaviventris ◽  
Fasting Period ◽  
Hormone Sensitive ◽  
Clear Increase

White adipose tissue (WAT) and plasma samples were obtained from yellow-bellied marmots (Marmota flaviventris) throughout the year. Mean plasma triacylglycerol (TG), free fatty acids (FFAs), and glycerol were determined. There was a clear increase in FFAs and decrease in mean TG and glycerol during the hibernation period when animals were fasting, suggesting increased lipolysis. RNA was isolated from WAT biopsies at four times in the year: spring, summer, fall, and winter. There were significant changes in the relative levels of mRNA for lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) during the body mass cycle of the marmot. The relative levels of LPL mRNA are high during the mass gain phase of the year and that of HSL mRNA are high during the fasting period when endogenous lipid is utilized. These results suggest that the genes for LPL and HSL are regulated seasonally to control the adipose mass depot in marmots.

scholarly journals Resveratrol-Induced White Adipose Tissue Browning in Obese Mice by Remodeling Fecal Microbiota

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3356 ◽  
Author(s):  
Weiyao Liao ◽  
Xiaohan Yin ◽  
Qingrong Li ◽  
Hongmin Zhang ◽  
Zihui Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Gut Microbiota ◽  
White Adipose Tissue ◽  
Additional Treatment ◽  
The Body ◽  
Sirtuin 1 ◽  
Obese Mice ◽  
Positive Role ◽  
White Fat

Promoting the browning of white fat may be a potential means of combating obesity. Therefore, in this study, we investigated the effect of resveratrol (RES) on the body weight and browning of white fat in high-fat diet (HFD)-induced obese mice and the potential associated mechanism in vivo. Eight-week-old male mice were randomized to receive different treatments: (1), chow without any additional treatment (chow); (2), chow plus 0.4% resveratrol (chow-RES); (3), HFD without any additional treatment (HFD); and (4), HFD plus 0.4% resveratrol (HFD-RES). After 4 weeks of feeding, additional 8-week-old male recipient mice were randomly allocated to the following 4 treatments: (5), HFD and received feces from chow-fed mice; (6), HFD and received feces from chow-RES-fed mice; (7), HFD and received feces from HFD-fed mice; and (8), HFD and received feces from HFD-RES-fed mice. RES treatment significantly inhibited increases in fat accumulation, promoted the browning of white adipose tissue (WAT) and alleviated gut microbiota dysbiosis in HFD-fed mice. Subsequent analyses showed that the gut microbiota remodeling induced by resveratrol had a positive role in WAT browning, and sirtuin-1 (Sirt1) signaling appears to be a key component of this process. Overall, the results show that RES may serve as a potential intervention to reduce obesity by alleviating dysbiosis of the gut microbiota.

scholarly journals Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1−/− Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1706-1716 ◽  
Author(s):  
Fen Xu ◽  
David Burk ◽  
Zhanguo Gao ◽  
Jun Yin ◽  
Xia Zhang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipocyte Differentiation ◽  
Nuclear Factor Κb ◽  
The Body ◽  
Sirtuin 1 ◽  
Vascular Density ◽  
Peroxisome Proliferator ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue.

Participation of ERα and ERβ in glucose homeostasis in skeletal muscle and white adipose tissue

2009 ◽  
Vol 297 (1) ◽  
pp. E124-E133 ◽  
Author(s):  
Rodrigo P. A. Barros ◽  
Chiara Gabbi ◽  
Andrea Morani ◽  
Margaret Warner ◽  
Jan-Åke Gustafsson
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Homeostasis ◽  
White Adipose Tissue ◽  
Glucose Transporter ◽  
Wild Type ◽  
Glut4 Expression ◽  
Glucose Challenge ◽  
Fasting Hypoglycemia

Glucose uptake and homeostasis are regulated mainly by skeletal muscle (SM), white adipose tissue (WAT), pancreas, and the liver. Participation of estradiol in this regulation is still under intense investigation. We have demonstrated that, in SM of male mice, expression of the insulin-regulated glucose transporter (GLUT)4 is reduced by estrogen receptor (ER)β agonists. In the present study, to investigate the relative contributions of ERα and ERβ in glucose homeostasis, we examined the effects of tamoxifen (Tam) on GLUT4 expression in SM and WAT in wild-type (WT) and ER−/− mice. ERβ−/− mice were characterized by fasting hypoglycemia, increased levels of SM GLUT4, pancreatic islet hypertrophy, and a belated rise in plasma insulin in response to a glucose challenge. ERα−/− mice, on the contrary, were hyperglycemic and glucose intolerant, and expression of SM GLUT4 was markedly lower than in WT mice. Tam had no effect on glucose tolerance or insulin sensitivity in WT mice. In ERα−/− mice, Tam increased GLUT4 and improved insulin sensitivity. i.e., it behaved as an ERβ antagonist in SM but had no effect on WAT. In ERβ−/− mice, Tam did not affect GLUT4 in SM but acted as an ERα antagonist in WAT, decreasing GLUT4. Thus, in the interplay between ERα and ERβ, ERβ-mediated repression of GLUT4 predominates in SM but ERα-mediated induction of GLUT4 predominates in WAT. This tissue-specific difference in dominance of one ER over the other is reflected in the ratio of the expression of the two receptors. ERα predominates in WAT and ERβ in SM.

scholarly journals Tributyrin in Inflammation: Does White Adipose Tissue Affect Colorectal Cancer?

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 110 ◽  
Author(s):  
Luana Amorim Biondo ◽  
Alexandre Abilio S. Teixeira ◽  
Loreana S. Silveira ◽  
Camila O. Souza ◽  
Raquel G. F. Costa ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Colon Carcinogenesis ◽  
Serum Glucose ◽  
Control Group ◽  
Chow Diet ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Factor Alpha

Colorectal cancer affects the large intestine, leading to loss of white adipose tissue (WAT) and alterations in adipokine secretion. Lower incidence of colorectal cancer is associated with increased fibre intake. Fructooligosaccharides (FOS) are fibres that increase production of butyrate by the intestinal microbiota. Tributyrin, a prodrug of butyric acid, exerts beneficial anti-inflammatory effects on colorectal cancer. Our aim was to characterise the effects of diets rich in FOS and tributyrin within the context of a colon carcinogenesis model, and characterise possible support of tumorigenesis by WAT. C57/BL6 male mice were divided into four groups: a control group (CT) fed with chow diet and three colon carcinogenesis-induced groups fed either with chow diet (CA), tributyrin-supplemented diet (BUT), or with FOS-supplemented diet. Colon carcinogenesis decreased adipose mass in subcutaneous, epididymal, and retroperitoneal tissues, while also reducing serum glucose and leptin concentrations. However, it did not alter the concentrations of adiponectin, interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNF)-α in WAT. Additionally, the supplements did not revert the colon cancer affected parameters. The BUT group exhibited even higher glucose tolerance and levels of IL-6, VEGF, and TNF-α in WAT. To conclude our study, FOS and butyrate supplements were not beneficial. In addition, butyrate worsened adipose tissue inflammation.

Sign in / Sign up

Export Citation Format

Share Document