Biomedical subjects

Mathias Fasshauer

Publications and source records attributed to Mathias Fasshauer.

At least 19 recordsLinked to original sources

PubMed2005

Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes.

Recently, adipose triglyceride lipase (ATGL, also called desnutrin and calcium-independent phospholipase A2 [iPLA(2)] zeta) was isolated as a novel adipose-expressed triglyceride lipase which is downregulated in obesity and may contribute to obesity-associated metabolic disorders such as hyperlipidemia and insulin resistance. To clarify expression and regulation of this fat-derived lipase, ATGL mRNA was measured in 3T3-L1 adipocytes by quantitative real-time reverse transcription-polymerase chain reaction after treatment with isoproterenol, tumor necrosis factor (TNF) alpha, insulin, and growth hormone (GH) which have been shown to influence lipolysis and insulin sensitivity profoundly. Interestingly, treatment of adipocytes with 100 nM isoproterenol, 30 ng/ml TNF alpha, and 100 nM insulin for 16 h significantly decreased ATGL mRNA to 74%, 17%, and 49% of control levels, respectively. GH did not influence ATGL synthesis. The effect of isoproterenol, TNFalpha, and insulin on ATGL expression was time- and dose-dependent. Similarly, HSL mRNA was downregulated by the three hormones. Furthermore, signaling studies suggested that activation of Gs-protein-coupled pathways by forskolin and cholera toxin is sufficient to significantly downregulate ATGL mRNA. Moreover, p44/42 mitogen-activated protein kinase appears to partly mediate the negative effect of insulin but not TNFalpha on ATGL. Taken together, downregulation of ATGL by isoproterenol, TNFalpha, and insulin might contribute to dysregulated expression and function of this lipase in obesity, hyperlipidemia, and insulin resistance.

3T3-L1 Cells↗

PubMed2005

Interleukin-6 is a negative regulator of visfatin gene expression in 3T3-L1 adipocytes.

Visfatin is a novel adipocytokine exerting insulin-mimetic effects in various insulin-sensitive tissues such as liver, muscle, and fat. In contrast, interleukin (IL)-6 is a proinflammatory adipose-secreted factor that induces insulin resistance and plasma concentrations that correlate with the development of type 2 diabetes mellitus. In the present study, the impact of IL-6 on visfatin gene expression in 3T3-L1 adipocytes was determined by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, 30 ng/ml IL-6 time-dependently downregulated visfatin synthesis with a significant 40% suppression seen after 4 h of treatment. Furthermore, the addition of IL-6 for 16 h dose-dependently suppressed visfatin mRNA with significant effects first observed at concentrations as low as 3 ng/ml and a maximal 43% reduction at 30 ng/ml effector. Moreover, inhibitor studies suggested that the negative effect of IL-6 on visfatin expression is, at least in part, mediated by p44/42 mitogen-activated protein kinase. In contrast, troglitazone did not reverse the negative effect of IL-6 on visfatin synthesis under these conditions. Taken together, our study suggests that IL-6 might influence glucose tolerance in part by regulation of the novel insulin-mimetic adipocytokine visfatin.

3T3-L1 Cells↗

PubMed2005

Regulation of adiponectin receptor R1 and R2 gene expression in adipocytes of C57BL/6 mice.

Adiponectin has gained significant attention as a mediator of insulin sensitivity. Recently, two receptors of this adipocyte-secreted hormone, adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2), have been cloned. To improve our understanding of the regulation of these receptors in adipocytes, AdipoR1 and AdipoR2 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction in brown adipocytes and adipocytes from epigonadal and subcutaneous adipose tissue of C57BL/6 mice as a function of feeding and circadian clocks. AdipoR1 gene expression was higher in brown adipose tissue and epigonadal adipose tissue, but lower in subcutaneous fat in fasted as compared to random-fed mice. In parallel, AdipoR2 mRNA levels were also higher in epigonadal adipose tissue of fasted as compared to fed mice, however, there was no regulation of AdipoR2 mRNA in brown and subcutaneous fat depending on the feeding state. Furthermore, AdipoR2 gene expression was significantly higher in epigonadal as compared to subcutaneous fat. Interestingly, a parallel circadian gene expression pattern for both AdipoR1 and AdipoR2 with lower expression between 20:00 and 06:00 h in brown, epigonadal, and subcutaneous adipose tissue was also found. In conclusion, our results suggest a fat depot specific regulation of AdipoR1 and AdipoR2 gene expression in brown and white fat by fasting. In addition, we have identified a coordinated circadian pattern of AdipoR1 and AdipoR2 gene expression in these tissues.

Adipocytes↗

PubMed2005

Therapeutic perspectives of adipocytokines.

Various adipocyte-secreted factors have been described which profoundly affect insulin sensitivity and might potentially link obesity, insulin resistance and cardiovascular disease. Among those, adiponectin, visfatin and omentin appear as insulin-sensitising adipocytokines, whereas TNF-alpha, IL-6 and resistin induce insulin resistance. Moreover, leptin is a fat-derived key regulator of appetite and energy expenditure. Due to their profound effect on whole-body glucose and energy metabolism, adipocytokines have attracted interest as potential new therapeutics for diabetes mellitus and obesity. The current knowledge on function, regulation and therapeutic potential of various adipocytokines, as well as their clinical implications, are discussed in this review.

Adipocytes↗

PubMed2005

Hormonal regulation of the novel adipocytokine visfatin in 3T3-L1 adipocytes.

Recently, visfatin was characterized as a novel adipo-cytokine that is upregulated in obesity and exerts insulin-mimetic effects in various tissues. To clarify expression and regulation of this adipocytokine, visfatin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction in 3T3-L1 adipocytes during adipogenesis and after treatment with various hormones known to alter insulin sensitivity. Visfatin expression was about 6-fold higher in 3T3-L1 adipocytes in vitro as compared with epididymal fat in vivo and increased during adipogenic conversion more than 3-fold. Interestingly, 100 nM dexamethasone significantly increased visfatin mRNA by almost 1.5-fold. In contrast, 500 ng/ml growth hormone (GH), 10 ng/ml tumor necrosis factor (TNF) alpha, and 10 microM isoproterenol downregulated visfatin expression by 45%, 36%, and 43% respectively. Insulin did not influence synthesis of this adipocytokine. The effects of dexamethasone, GH, TNFalpha and isoproterenol were time- and dose-dependent. Furthermore, activation of G(s)-protein-coupled pathways by forskolin and cholera toxin was sufficient to significantly downregulate visfatin mRNA. Taken together, our results show a differential regulation of visfatin mRNA by insulin resistance-inducing hormones, supporting the view that this adipo-cytokine might be an interesting novel candidate linking core components of the metabolic syndrome such as obesity and insulin resistance.

3T3-L1 Cells↗

PubMed2004

Ciliary neurotrophic factor influences endocrine adipocyte function: inhibition of leptin via PI 3-kinase.

Ciliary neurotrophic factor (CNTF), originally known for its involvement in the modulation of neuronal growth, has been discovered to exert anorexigenic effects and is currently being investigated in clinical studies for the treatment of obesity and insulin resistance. This neuropeptide acts on the central nervous system. However, we have recently demonstrated direct peripheral effects on adipocyte signalling and thermogenesis. Given the emerging endocrine role of adipose tissue in the regulation of energy homeostasis and insulin resistance, we investigated potential effects of CNTF on leptin expression and secretion. Our study demonstrates a direct inhibition of leptin expression and secretion by acute and chronic CNTF treatment. Furthermore, we demonstrate a differentiation- and Janus kinase 2 (JAK2)-independent, but phosphatidylinositol 3-kinase-dependent signalling pathway mediating this negative effect. These results provide novel evidence for a role of CNTF in the selective modulation of adipocyte endocrine function which may have important implications for the regulation of energy homeostasis.

Adipocytes↗

PubMed2004

Monocyte chemoattractant protein 1 expression is stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes.

During the last 10 years, various adipocytokines have been described which influence insulin sensitivity profoundly and might, therefore, potentially link obesity and insulin resistance. Recently, monocyte chemoattractant protein (MCP)-1 was characterized as a novel adipose-secreted factor upregulated in obesity and insulin resistance that impairs insulin signaling in fat cells in vitro and can be found in atherosclerotic lesions. To clarify expression and regulation of this adipocytokine, MCP-1 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance. Interestingly, MCP-1 synthesis was significantly downregulated between 43% and 68% during differentiation of 3T3-L1 preadipocytes. Furthermore, 10 ng/ml tumor necrosis factor alpha, 100 nM insulin, 500 ng/ml growth hormone (GH), and 30 ng/ml interleukin (IL)-6-induced MCP-1 mRNA by up to 124-, 23-, 8-, and 2.5-fold, respectively, in a time-dependent fashion with significant stimulation seen at concentrations as low as 0.5 ng/ml GH and 30 ng/ml IL-6. In contrast, the glucocorticoid dexamethasone potently downregulated MCP-1 with significant suppression detectable at concentrations as low as 3 nM and as early as 2h after effector addition. Studies using pharmacological inhibitors suggested that the positive effects of GH and IL-6 on MCP-1 synthesis are at least in part mediated by janus kinase 2 and p44/42 mitogen-activated protein kinase. Taken together, our results show a differential regulation of MCP-1 mRNA by insulin resistance-inducing hormones and support the view that this adipocytokine might be an interesting novel candidate linking insulin resistance, obesity, and atherosclerosis. This adipocytokine could thus be a potential pharmacological target for the treatment of impaired insulin sensitivity.

3T3 Cells↗

PubMed2004

Interleukin-6 is a positive regulator of tumor necrosis factor alpha-induced adipose-related protein in 3T3-L1 adipocytes.

Tumor necrosis factor (TNF) alpha-induced adipose-related protein (TIARP) is a novel TNFalpha-stimulated protein in adipocytes. Besides TNFalpha, interleukin (IL)-6 has recently been shown to be another adipocytokine implicated in insulin resistance. Therefore, the impact of IL-6 on TIARP gene expression in 3T3-L1 adipocytes was determined by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, TIARP mRNA expression was stimulated up to 3.8-fold by IL-6 in a dose-dependent fashion with significant stimulation detectable at effector concentrations as low as 3 ng/ml and maximal effects seen at 100 ng/ml IL-6. Induction of TIARP mRNA by IL-6 was time-dependent with significant upregulation occurring as early as 2 h after effector addition and maximal effects observed at 4 h. In parallel, TIARP protein synthesis was upregulated with maximal effects seen after 8 h of IL-6 treatment. Furthermore, the Janus kinase 2 inhibitor AG490 decreased TIARP mRNA expression. The increase of TIARP mRNA could be reversed by withdrawal of IL-6 for 24 h. Furthermore, TIARP mRNA induction by IL-6 was also seen in brown adipocytes but not in muscle and liver cells. Taken together, these results show that TIARP is acutely regulated in adipose tissue not only by TNFalpha but also by IL-6 which has been shown to be another important cytokine implicated in the pathogenesis of insulin resistance.

3T3-L1 Cells↗

PubMed2004

Growth hormone is a positive regulator of adiponectin receptor 2 in 3T3-L1 adipocytes.

The fat-derived protein adiponectin is an important insulin-sensitizing adipocytokine which is downregulated in insulin resistance and obesity. Recently, two receptors of this adipose-expressed protein called adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) have been cloned. To clarify expression and regulation of these receptors in fat cells, AdipoR1 and AdipoR2 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance. Interestingly, AdipoR2 synthesis was significantly increased up to 4.8-fold during differentiation of 3T3-L1 preadipocytes, whereas AdipoR1 expression was only augmented up to 1.4-fold. Furthermore, growth hormone (GH) induced AdipoR2, but not AdipoR1 mRNA by up to 2.4-fold in a dose- and time-dependent fashion with significant stimulation detectable at concentrations as low as 5 ng/ml GH and as early as 2 h after effector addition. The positive effect of GH on AdipoR2 expression could be reversed by withdrawal of the hormone for 24 h. In contrast, other key hormones involved in the regulation of insulin resistance and energy metabolism such as insulin, isoproterenol, dexamethasone, triiodothyronine, angiotensin 2, tumor necrosis factor alpha, and interleukin-6 did not influence AdipoR1 and AdipoR2 synthesis in vitro. Taken together, our results suggest that AdipoR2 expression is differentiation-dependent and selectively regulated by GH implying a potential role of this hormone in adiponectin-associated alterations of insulin sensitivity and energy homeostasis.

3T3 Cells↗

PubMed2004

Adiponectin, obesity, and cardiovascular disease.

Several adipocyte-secreted factors have been demonstrated to potentially link obesity, insulin resistance, and cardiovascular disease. Among those, adiponectin is an insulin-sensitizing and anti-inflammatory adipokine, concentrations of which are decreased in obesity-associated metabolic and vascular disorders. Recently, two adiponectin receptors (AdipoR) have been isolated and adenosine monophosphate kinase (AMPK), as well as acetyl coenzyme A carboxylase (ACC), appear to be critical downstream mediators for various effects of this adipokine. In addition to beneficial metabolic effects, adiponectin seems to be vasoprotective by interfering with various atherogenic processes. Of clinical interest, thiazolidinediones (TZDs) which are used in the treatment of type 2 diabetes stimulate adiponectin expression and secretion whereas several hormones dysregulated in insulin resistance and obesity downregulate this adipokine. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review and its clinical implications are discussed.

Acetyl-CoA Carboxylase↗

PubMed2004

Comparative analysis of conventional and an adaptive computer-based hypoglycaemia education programs.

Adaptive interactive computer-based education programs which can be personalized to patients' needs and skills might be more suitable for patients' training as compared to conventional ones. We tested whether there are differences between an adaptive and a conventional version of a computer-based hypoglycaemia education program concerning successful training and user friendliness. One hundred and twenty randomized diabetic patients were enrolled in this study. The two different programs were compared by using the following criteria: (1) the number of actions needed to get out of or prevent hypoglycaemia, (2) the need for external help, (3) the average time needed for completing one task and (4) user friendliness as determined by a questionnaire. Patients using the adaptive computer-based hypoglycaemia education program needed less actions to get out of or prevent hypoglycaemia, less external help and less time to finish tasks. Furthermore, the user friendliness of the adaptive computer program received a significantly better rating by the patients. The adaptive computer-based hypoglycaemia education program shows significantly better results as compared to a conventional one. Therefore, using adaptive computer-based programs might be helpful for education of patients.

Attitude to Computers↗

PubMed2004

Comparative analysis of conventional training and a computer-based interactive training program for celiac disease patients.

Gluten-free diet (GFD) protects against the complications of celiac disease (CD). However, training in the dietetic field is rare in Germany. Thus, CD patients are likely to benefit from a computer-based interactive training program (CBITP) combined with interactive exercises. We compared a CBITP and a conventional training for CD patients regarding increased knowledge, transferability and sustainability. In that context we analyzed whether CD patients are more able to judge the risk of a food or a situation after practicing with the interactive training software. Sixty-four CD patients were included and randomized in two groups. While the first group used the CBITP, the control group received written instructions. Before and after taking part in the training program and 3 weeks later, the participants filled in a questionnaire for celiac knowledge. The results show that both intervention and control groups increased knowledge about CD. However, the intervention group showed significantly better outcome. A CBITP significantly increases knowledge and sustainability as compared to a conventional training for CD patients. CBITPs can enhance patients' training and treatment.

Adult↗

PubMed2004

Metformin inhibits leptin secretion via a mitogen-activated protein kinase signalling pathway in brown adipocytes.

Metformin is an anti-diabetic drug with anorexigenic properties. The precise cellular mechanisms of its action are not entirely understood. Adipose tissue has recently been recognized as an important endocrine organ that is pivotal for the regulation of insulin resistance and energy homeostasis. Due to its thermogenic capacity brown adipose tissue contributes to the regulation of energy metabolism and is an attractive target tissue for pharmacological approaches to treating insulin resistance and obesity. Leptin is the prototypic adipocyte-derived hormone inducing a negative energy balance. We investigated effects of metformin on adipocyte metabolism, signalling, and leptin secretion in a brown adipocyte model. Metformin acutely stimulated p44/p42 mitogen-activated protein (MAP) kinase in a dose- (3.2-fold at 1 mmol/l, P< 0.05) as well as time-dependent (3.8-fold at 5 min, P< 0.05) manner. This stimulation was highly selective since phosphorylation of intermediates in the stress kinase, janus kinase (JAK)-signal transducer and activator of transcription (STAT), and phosphatidylinositol (PI) 3-kinase signalling pathways such as p38 MAP kinase, STAT3, and Akt was unaltered. Furthermore, chronic metformin treatment for 12 days dose-dependently inhibited leptin secretion by 35% and 75% at 500 mumol/l and 1 mmol/l metformin respectively (P< 0.01). This reduction was not caused by alterations in adipocyte differentiation. Moreover, the impairment in leptin secretion by metformin was reversible within 48 h after removal of the drug. Pharmacological inhibition of p44/p42 MAP kinase prevented the metformin-induced negative effect on leptin secretion. Taken together, our data demonstrate direct acute effects of metformin on adipocyte signalling and endocrine function with robust inhibition of leptin secretion. They suggest a selective molecular mechanism that may contribute to the anorexigenic effect of this antidiabetic compound.

Adipocytes↗

PubMed2004

Serum amyloid A3 expression is stimulated by dexamethasone and interleukin-6 in 3T3-L1 adipocytes.

A chronic increase in systemic levels of acute-phase reactants contributes to the development of insulin resistance and associated disorders such as cardiovascular disease. Recently, serum amyloid A3 (SAA3) has been characterized as an adipocyte-secreted acute-phase reactant, expression of which is dramatically increased in insulin resistance and obesity. To further clarify expression and regulation of this adipocytokine in fat, SAA3 mRNA was measured by quantitative real-time reverse transcriptase PCR during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance and contribute to atherosclerosis. SAA3 mRNA was dramatically induced up to 77-fold during differentiation of 3T3-L1 preadipocytes. Furthermore, 100 nM dexamethasone and 30 ng/ml interleukin (IL)-6 induced SAA3 mRNA by up to 11- and 4.8-fold, respectively, in a time-dependent fashion with significant stimulation observed at concentrations as low as 10 nM dexamethasone and 1 ng/ml IL-6. In contrast, insulin, isoproterenol and growth hormone did not influence SAA3 synthesis. Inhibitor studies suggested that the positive effect of IL-6 on SAA3 expression is at least in part mediated by Janus kinase 2. Taken together, our results show a differential regulation of SAA3 by glucocorticoids and IL-6 supporting an integrative role of this acute-phase reactant in the pathogenesis of insulin resistance and its link to obesity and cardiovascular disease.

3T3-L1 Cells↗

PubMed2003

Positive and negative roles of p85 alpha and p85 beta regulatory subunits of phosphoinositide 3-kinase in insulin signaling.

Class IA phosphoinositide (PI) 3-kinase is composed of a p110 catalytic subunit and a p85 regulatory subunit and plays a pivotal role in insulin signaling. To explore the physiological roles of two major regulatory isoforms, p85 alpha and p85 beta, we have established brown adipose cell lines with disruption of the Pik3r1 or Pik3r2 gene. Pik3r1-/- (p85 alpha-/-) cells show a 70% reduction of p85 protein and a parallel reduction of p110. These cells have a 50% decrease in PI 3-kinase activity and a 30% decrease in Akt activity, leading to decreased insulin-induced glucose uptake and anti-apoptosis. Pik3r2-/- (p85 beta-/-) cells show a 25% reduction of p85 protein but normal levels of p85-p110 and PI 3-kinase activity, supporting the fact that p85 is more abundant than p110 in wild type. p85 beta-/- cells, however, exhibit significantly increased insulin-induced Akt activation, leading to increased anti-apoptosis. Reconstitution experiments suggest that the discrepancy between PI 3-kinase activity and Akt activity is at least in part due to the p85-dependent negative regulation of downstream signaling of PI 3-kinase. Indeed, both p85 alpha-/- cells and p85 beta-/- cells exhibit significantly increased insulin-induced glycogen synthase activation. p85 alpha-/- cells show decreased insulin-stimulated Jun N-terminal kinase activity, which is restored by expression of p85 alpha, p85 beta, or a p85 mutant that does not bind to p110, indicating the existence of p85-dependent, but PI 3-kinase-independent, signaling pathway. Furthermore, a reduction of p85 beta specifically increases insulin receptor substrate-2 phosphorylation. Thus, p85 alpha and p85 beta modulate PI 3-kinase-dependent signaling by multiple mechanisms and transmit signals independent of PI 3-kinase activation.

Adenoviridae↗

PubMed2003

Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes.

Recently, it has been shown that adiponectin is an important insulin-sensitizing fat-derived protein which is downregulated in insulin resistance and obesity, and replenishment of which improves insulin sensitivity. In contrast, interleukin (IL)-6 appears as an adipocytokine serum concentrations of which are elevated in these states. However, it has not been determined whether IL-6 might impact on expression and secretion of adiponectin. To clarify this, 3T3-L1 adipocytes were treated with different concentrations of IL-6 for various periods of time. Adiponectin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction and secretion was determined by radioimmunoassays. Interestingly, treatment of 3T3-L1 cells with 30 ng/ml IL-6 significantly decreased adiponectin secretion to 75% of control levels. Adiponectin secretion was also inhibited between 25% and 45% by chronic treatment with forskolin (50 microM), tumor necrosis factor alpha (100 ng/ml), and dexamethasone (100 nM). Furthermore, adiponectin mRNA expression was downregulated by up to 50% in a time- and dose-dependent manner, with significant inhibition detectable at concentrations as low as 3 ng/ml IL-6 and as early as 8h after effector addition. The inhibitory effect of IL-6 was partially reversed by pretreatment of 3T3-L1 cells with pharmacological inhibitors of a p44/42 mitogen-activated protein (MAP) kinase. Moreover, the negative effect of IL-6 on adiponectin mRNA expression could be reversed by withdrawal of the hormone for 24h. Taken together, our results suggest that adiponectin gene expression is reversibly downregulated by IL-6 and support the concept of adiponectin being an important selectively controlled modulator of insulin sensitivity.

3T3 Cells↗

PubMed2002

Hormonal regulation of adiponectin gene expression in 3T3-L1 adipocytes.

Recently, it has been demonstrated that the fat-derived protein adiponectin is an important insulin-sensitizing adipocytokine which is downregulated in insulin resistance and obesity and replenishment of which in adiponectin-deficient states improves insulin sensitivity. To clarify the regulation of adiponectin gene expression, 3T3-L1 adipocytes were treated with various hormones known to induce insulin resistance in vivo and adiponectin mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction. Interestingly, treatment of 3T3-L1 cells with 100 nM insulin, 10 ng/ml tumor necrosis factor (TNF) alpha, or 100 nM dexamethasone for 16 h suppressed adiponectin gene expression by about 50 to 85% while angiotensin 2, growth hormone, and triiodothyronine did not have any effect. Furthermore, insulin reduced the level of adiponectin mRNA in a dose- and time-dependent fashion with inhibition detectable at concentrations as low as 10 nM insulin and as early as 4 h after effector addition. The inhibitory effect of insulin was partially reversed by pretreatment of 3T3-L1 cells with pharmacological inhibitors of p44/42 mitogen-activated protein (MAP) kinase, phosphatidylinositol (PI) 3-kinase, and p70S6 kinase. Moreover, the negative effects of insulin, TNFalpha, and dexamethasone on adiponectin gene expression could be completely reversed by withdrawal of the hormones for 24 h. Taken together, our results suggest that adiponectin gene expression is reversibly downregulated by insulin, TNFalpha, and dexamethasone. The data support the concept of adiponectin being an important selectively controlled modulator of insulin sensitivity.

3T3 Cells↗

PubMed2002

Novel adipocyte lines from brown fat: a model system for the study of differentiation, energy metabolism, and insulin action.

Adipose tissue has emerged as an important endocrine regulator of glucose metabolism and energy homeostasis. By virtue of the mitochondrial protein uncoupling protein-1 (UCP-1), brown fat additionally plays a unique role in thermoregulation. Interest has focused on this tissue not only as a target for pharmacotherapy of obesity and insulin resistance but also as an endocrine tissue with leptin secretion and high insulin sensitivity. Most studies of adipocytes have been limited either to primary cell culture or to a small number of established cell lines. Recently, we have generated immortalized brown adipocyte cell lines from single newborn mice of different knockout mouse models. These cell lines retain the main characteristics of primary cells including UCP-1 expression. They display sensitive and diverse metabolic responses to insulin and adrenergic stimulation and have proven to be useful in the characterization of UCP regulation and the role of key insulin signaling elements for insulin action. Here, we outline common approaches to the generation of adipose tissue cell lines. Furthermore, we propose that the novel technique of generating brown adipocyte lines from a single newborn mouse will be instrumental in gaining further insight into the role of a broad range of signaling molecules in adipose tissue biology and in the pathogenesis of insulin resistance.

Adipocytes↗