scholarly journals A method to quantify glucose utilization in vivo in skeletal muscle and white adipose tissue of the anaesthetized rat

1985 ◽  
Vol 228 (1) ◽  
pp. 103-110 ◽  
Author(s):  
P Ferré ◽  
A Leturque ◽  
A F Burnol ◽  
L Penicaud ◽  
J Girard
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Glucose Utilization ◽  
Correction Factors ◽  
Arterial Blood ◽  
Time Period ◽  
Anaesthetized Rat

A quantitative method allowing determination of glucose metabolism in vivo in muscles and white adipose tissue of the anaesthetized rat is presented. A tracer dose of 2-deoxy[3H]glucose was injected intravenously in an anaesthetized rat and the concentration of 2-deoxy[3H]glucose was monitored in arterial blood. After 30-80 min, three muscles, the soleus, the extensor digitorum longus and the epitrochlearis, periovarian white adipose tissue and brain were sampled and analysed for their content of 2-deoxy[3H]glucose 6-phosphate. This content could be related to glucose utilization during the same time period, since (1) the integral of the decrease of 2-deoxy[3H]glucose in arterial blood was known and (2) correction factors for the analogue effect of 2-deoxyglucose compared with glucose in the transport and phosphorylation steps were determined from experiments in vitro. Glucose utilization was then measured by this technique in the tissues of post-absorptive rats in the basal state (0.1 munit of insulin/ml of plasma) or during euglycaemic-hyperinsulinaemic glucose clamp (8 munits of insulin/ml of plasma) and of 48 h-starved rats. Results corresponded qualitatively and quantitatively to the known physiological characteristics of the tissues studied.

Overexpression of a short human seipin/BSCL2 isoform in mouse adipose tissue results in mild lipodystrophy

2012 ◽  
Vol 302 (6) ◽  
pp. E705-E713 ◽  
Author(s):  
Xin Cui ◽  
Yuhui Wang ◽  
Lingjun Meng ◽  
Weihua Fei ◽  
Jingna Deng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Transgenic Mice ◽  
White Adipose Tissue ◽  
Loss Of Function ◽  
Gene Encoding ◽  
Triacylglycerol Content ◽  
Adipocyte Development

Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is a recessive disorder characterized by an almost complete loss of adipose tissue, insulin resistance, and fatty liver. BSCL2 is caused by loss-of-function mutations in the BSCL2/seipin gene, which encodes seipin. The essential role for seipin in adipogenesis has recently been established both in vitro and in vivo. However, seipin is highly upregulated at later stages of adipocyte development, and its role in mature adipocytes remains to be elucidated. We therefore generated transgenic mice overexpressing a short isoform of human BSCL2 gene (encoding 398 amino acids) using the adipocyte-specific aP2 promoter. The transgenic mice produced ∼150% more seipin than littermate controls in white adipose tissue. Surprisingly, the increased expression of seipin markedly reduced the mass of white adipose tissue and the size of adipocytes and lipid droplets. This may be due in part to elevated lipolysis rates in the transgenic mice. Moreover, there was a nearly 50% increase in the triacylglycerol content of transgenic liver. These results suggest that seipin promotes the differentiation of preadipocytes but may inhibit lipid storage in mature adipocytes.

scholarly journals Metabolic consequences of hyperinsulinaemia imposed on normal rats on glucose handling by white adipose tissue, muscles and liver

1990 ◽  
Vol 267 (1) ◽  
pp. 99-103 ◽  
Author(s):  
I Cusin ◽  
J Terrettaz ◽  
F Rohner-Jeanrenaud ◽  
B Jeanrenaud
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Glucose Utilization ◽  
Insulin Treatment ◽  
Driving Forces ◽  
Hepatic Glucose Production ◽  
Lipid Synthesis ◽  
Liver Fat ◽  
Insulin Responsiveness

The effects of hyperinsulinaemia imposed on normal rats on the subsequent insulin-responsiveness in vivo of 2-deoxy-D-glucose uptake of white adipose tissue and of various muscle types were investigated. This was done by treating normal rats with insulin via osmotic minipumps, and by comparing them with saline-infused controls. Hyperinsulinaemia produced by prior insulin treatment resulted in a well-tolerated hypoglycaemia. At the end of the treatment, the glucose utilization index of individual tissues was determined by euglycaemic/hyperinsulinaemic clamps associated with the labelled 2-deoxy-D-glucose method. Prior insulin treatment resulted in increased insulin-responsiveness of the glucose utilization index of white adipose tissue, and in increased total lipogenesis in white adipose tissue and fat-pad weight. In contrast, prior insulin treatment resulted in a decreased glucose utilization index of several muscles. These opposite effects of hyperinsulinaemia on glucose utilization in white adipose tissue and muscles persisted when the hypoglycaemia-induced catecholamine output was prevented (adrenomedullectomy, propranolol treatment), as well as when hypoglycaemia was normalized by concomitant insulin treatment and glucose infusion. Insulin suppressed hepatic glucose production during the clamps in insulin-treated rats as in the respective controls, whereas total hepatic lipid synthesis and liver fat content were greater in rats treated with insulin than in controls. It is concluded that hyperinsulinaemia itself could be one of the driving forces responsible for producing increased glucose utilization by white adipose tissue, increased total lipid synthesis with fat accumulation in adipose tissue and the liver, together with an insulin-resistant state at the muscular level.

scholarly journals Hyperinsulinaemia increases insulin action in vivo in white adipose tissue but not in muscles

1990 ◽  
Vol 272 (1) ◽  
pp. 255-257 ◽  
Author(s):  
F Takao ◽  
M C Laury ◽  
A Ktorza ◽  
L Picon ◽  
L Pénicaud
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Skeletal Muscles ◽  
Insulin Action ◽  
Glucose Utilization ◽  
Rat Tissues ◽  
Hyperinsulinaemic Clamp ◽  
Euglycaemic Hyperinsulinaemic Clamp

The effect of 4 days of stable hyperglycaemia and resulting hyperinsulinaemia on insulin-induced glucose utilization by individual rat tissues was studied in vivo. The treatment produced a net increase in the glucose utilization index under both basal and insulin-stimulated (euglycaemic/hyperinsulinaemic clamp) conditions in white adipose tissue. On the contrary, glucose utilization was unchanged in aerobic muscles but was decreased in glycolytic skeletal muscles during the clamp.

scholarly journals Transcription Factor E2F1 Knockout Promotes Mice White Adipose Tissue Browning Through Autophagy Inhibition

2021 ◽  
Vol 12 ◽  
Author(s):  
Mingchen Xiong ◽  
Weijie Hu ◽  
Yufang Tan ◽  
Honghao Yu ◽  
Qi Zhang ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Underlying Mechanism ◽  
Metabolic Complications ◽  
Autophagy Inhibition ◽  
Transcription Factor E2f1

Obesity is associated with energy metabolic disturbance and is caused by long-term excessive energy storage in white adipose tissue (WAT). The WAT browning potentially reduces excessive energy accumulation, contributing an attractive target to combat obesity. As a pivotal regulator of cell growth, the transcription factor E2F1 activity dysregulation leads to metabolic complications. The regulatory effect and underlying mechanism of E2F1 knockout on WAT browning, have not been fully elucidated. To address this issue, in this study, the in vivo adipose morphology, mitochondria quantities, uncoupling protein 1 (UCP-1), autophagy-related genes in WAT of wild-type (WT) and E2F1–/– mice were detected. Furthermore, we evaluated the UCP-1, and autophagy-related gene expression in WT and E2F1–/– adipocyte in vitro. The results demonstrated that E2F1 knockout could increase mitochondria and UCP-1 expression in WAT through autophagy suppression in mice, thus promoting WAT browning. Besides, adipocytes lacking E2F1 showed upregulated UCP-1 and downregulated autophagy-related genes expression in vitro. These results verified that E2F1 knockout exerted effects on inducing mice WAT browning through autophagy inhibition in vivo and in vitro. These findings regarding the molecular mechanism of E2F1-modulated autophagy in controlling WAT plasticity, provide a novel insight into the functional network with the potential therapeutic application against obesity.

Control of glyceroneogenic activity in rat brown adipose tissue

2003 ◽  
Vol 285 (1) ◽  
pp. R177-R182 ◽  
Author(s):  
W. T. L. Festuccia ◽  
N. H. Kawashita ◽  
M. A. R. Garofalo ◽  
M. A. F. Moura ◽  
S. R. C. Brito ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Glucose Utilization ◽  
Streptozotocin Diabetes ◽  
Sympathetic Control ◽  
Balanced Diet ◽  
Threefold Increase ◽  
Brown Adipose

Brown adipose tissue (BAT) glyceroneogenesis was evaluated in rats either fasted for 48 h or with streptozotocin-diabetes induced 3 days previously or adapted for 20 days to a high-protein, carbohydrate-free (HP) diet, conditions in which BAT glucose utilization is reduced. The three treatments induced an increase in BAT glyceroneogenic activity, evidenced by increased rates of incorporation of [1-14C]pyruvate into triacylglycerol (TAG)-glycerol in vitro and a marked, threefold increase in the activity of BAT phospho enolpyruvate carboxykinase (PEPCK). BAT glycerokinase activity was not significantly affected by fasting or diabetes. After unilateral BAT denervation of rats fed either the HP or a balanced diet, glyceroneogenesis activity increased in denervated pads, evidenced by increased rates of nonglucose carbon incorporation into TAG-glycerol in vivo (difference between 3H2O and [14C]glucose incorporations) and of [1-14C]pyruvate in vitro. PEPCK activity was not significantly affected by denervation. The data suggest that BAT glyceroneogenesis is not under sympathetic control but is sensitive to hormonal/metabolic factors. In situations of reduced glucose use there is an increase in BAT glyceroneogenesis that may compensate the decreased generation of glycerol-3-phosphate from the hexose.

Production of glutamine and utilization of glutamate by rat subcutaneous adipose tissue in vivo

1994 ◽  
Vol 266 (1) ◽  
pp. E151-E154 ◽  
Author(s):  
T. J. Kowalski ◽  
M. Watford
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Sampling Technique ◽  
Calibration Method ◽  
Glutamine Metabolism ◽  
Whole Body ◽  
Arterial Blood ◽  
Subcutaneous Adipose

Information about adipose tissue amino acid metabolism is limited, with most data derived from studies in vitro. The purpose of this study was to further characterize the role of adipose tissue in glutamine metabolism in the rat in vivo. The extracellular concentrations of glutamine, glutamate, alanine, and ammonia were measured in the rat inguinal fat pad using a microdialysis sampling technique. A calibration method was used to accurately assess the extracellular levels of metabolites, and a comparison of these concentrations with those in arterial blood allowed determination of the net flux of each compound. The adipose tissue-arterial blood concentration differences were 122 +/- 19, 54 +/- 37, -61 +/- 21, and -28 +/- 13 microM for glutamine, alanine, glutamate, and ammonia, respectively, indicating a production of glutamine and an uptake of glutamate by subcutaneous adipose tissue. The magnitude of glutamine production suggests that adipose tissue may play a significant role in whole body glutamine homeostasis.

scholarly journals Adipogenic role of alternatively activated macrophages in β-adrenergic remodeling of white adipose tissue

2016 ◽  
Vol 310 (1) ◽  
pp. R55-R65 ◽  
Author(s):  
Yun-Hee Lee ◽  
Sang-Nam Kim ◽  
Hyun-Jung Kwon ◽  
Krishna Rao Maddipati ◽  
James G. Granneman
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
De Novo ◽  
Flow Cytometric Analysis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Physical Relationship ◽  
Alternatively Activated Macrophages

De novo brown adipogenesis involves the proliferation and differentiation of progenitors, yet the mechanisms that guide these events in vivo are poorly understood. We previously demonstrated that treatment with a β3-adrenergic receptor (ADRB3) agonist triggers brown/beige adipogenesis in gonadal white adipose tissue following adipocyte death and clearance by tissue macrophages. The close physical relationship between adipocyte progenitors and tissue macrophages suggested that the macrophages that clear dying adipocytes might generate proadipogenic factors. Flow cytometric analysis of macrophages from mice treated with CL 316,243 identified a subpopulation that contained elevated lipid and expressed CD44. Lipidomic analysis of fluorescence-activated cell sorting-isolated macrophages demonstrated that CD44+ macrophages contained four- to five-fold higher levels of the endogenous peroxisome-proliferator activated receptor gamma (PPARγ) ligands 9-hydroxyoctadecadienoic acid (HODE), and 13-HODE compared with CD44− macrophages. Gene expression profiling and immunohistochemistry demonstrated that ADRB3 agonist treatment upregulated expression of ALOX15, the lipoxygenase responsible for generating 9-HODE and 13-HODE. Using an in vitro model of adipocyte efferocytosis, we found that IL-4-primed tissue macrophages accumulated lipid from dying fat cells and upregulated expression of Alox15. Furthermore, treatment of differentiating adipocytes with 9-HODE and 13-HODE potentiated brown/beige adipogenesis. Collectively, these data indicate that noninflammatory removal of adipocyte remnants and coordinated generation of PPARγ ligands by M2 macrophages provides localized adipogenic signals to support de novo brown/beige adipogenesis.

scholarly journals Role of Exchange Protein Directly Activated by Cyclic AMP Isoform 1 in Energy Homeostasis: Regulation of Leptin Expression and Secretion in White Adipose Tissue

2016 ◽  
Vol 36 (19) ◽  
pp. 2440-2450 ◽  
Author(s):  
Yaohua Hu ◽  
William G. Robichaux ◽  
Fang C. Mei ◽  
Eun Ran Kim ◽  
Hui Wang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Cyclic Amp ◽  
Glucose Homeostasis ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Leptin Sensitivity ◽  
Leptin Expression

Epacs (exchange proteins directly activated by cyclic AMP [cAMP]) act as downstream effectors of cAMP and play important roles in energy balance and glucose homeostasis. While global deletion of Epac1 in mice leads to heightened leptin sensitivity in the hypothalamus and partial protection against high-fat diet (HFD)-induced obesity, the physiological functions of Epac1 in white adipose tissue (WAT) has not been explored. Here, we report that adipose tissue-specific Epac1 knockout (AEKO) mice are more prone to HFD-induced obesity, with increased food intake, reduced energy expenditure, and impaired glucose tolerance. Despite the fact that AEKO mice on HFD display increased body weight, these mice have decreased circulating leptin levels compared to their wild-type littermates.In vivoandin vitroanalyses further reveal that suppression of Epac1 in WAT decreases leptin mRNA expression and secretion by inhibiting cAMP response element binding (CREB) protein and AKT phosphorylation, respectively. Taken together, our results demonstrate that Epac1 plays an important role in regulating energy balance and glucose homeostasis by promoting leptin expression and secretion in WAT.

Beiging of white adipose tissue as a therapeutic strategy for weight loss in humans

2017 ◽  
Vol 31 (2) ◽  
Author(s):  
Baskaran Thyagarajan ◽  
Michelle T. Foster
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
Fat Utilization ◽  
Drug Molecules ◽  
Brown Adipose ◽  
And Storage

AbstractAn imbalance between energy intake and expenditure leads to obesity. Adiposity associated with obesity progressively causes inflammation, type 2 diabetes, hypertension, hyperlipidemia and cardiovascular disease. Excessive dietary intake of fat results in its accumulation and storage in the white adipose tissue (WAT), whereas energy expenditure by fat utilization and oxidation predominately occurs in the brown adipose tissue (BAT). Recently, the presence of a third type of fat, referred to as beige or brite (brown in white), has been recognized in certain kinds of WAT depots. It has been suggested that WAT can undergo the process of browning in response to stimuli that induce and enhance the expression of thermogenes characteristic of those typically associated with brown fat. The resultant beige or brite cells enhance energy expenditure by reducing lipids stored within adipose tissue. This has created significant excitement towards the development of a promising strategy to induce browning/beiging in WAT to combat the growing epidemic of obesity. This review systematically describes differential locations and functions of WAT and BAT, mechanisms of beiging of WAT and a concise analysis of drug molecules and natural products that activate the browning phenomenon in vitro and in vivo. This review also discusses potential approaches for targeting WAT with compounds for site-specific beiging induction. Overall, there are numerous mechanisms that govern browning of WAT. There are a variety of newly identified targets whereby potential molecules can promote beiging of WAT and thereby combat obesity.

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