The role of TNFα in adipocyte metabolism

Sethi, J.; Hotamışlıgil, Gökhan S.

doi:10.1006/scdb.1998.0273

Cited by 388 publications

(273 citation statements)

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“…[13][14][15] (b) FAs, either from stored TGs or from de novo synthesis in the WAT, are known to have signalling properties that can affect insulin sensitivity and contribute directly to lipotoxicity. 16 A key transcription factor for regulating FA metabolism, sterol regulatory element-binding protein 1 (SREBP1), may be a key molecule for the development of lipotoxicity.…”

Section: Experimental Paradigms To Study Lipotoxicitymentioning

confidence: 99%

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

2004

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Obesity and type 2 diabetes mellitus are the major noncommunicable public health problem of the 21st century. The best strategy to tackle this problem is to develop strategies to prevent/treat obesity. However, it is becoming clear that despite successful research identifying weight regulatory pathways, the development of the obesity epidemic is outpacing scientific progress. The lack of success controlling the obesity epidemic in an aging population will result in another subsequent uncontrolled epidemic of complications. Our research focuses on the mechanisms causing lipotoxicity aiming to identify suitable strategies to prevent or at least retard the development of the metabolic syndrome. Previous work using transgenic and knockout mouse models has shown an interplay between white adipose tissue and skeletal muscle linking fatty acid (FA) synthesis with reciprocal effects on FA oxidation. Work from our lab and others suggests that defective adipose tissue is a key link between obesity, insulin resistance and type 2 diabetes mellitus by promoting the development of lipotoxicity in peripheral tissues. We propose a series of models to describe the process by which the adipose tissue could react to an energy-rich environment and responds depending on genetic and physiological factors, impacting on the functions of other peripheral tissues. We suggest that by examining hypotheses that encompass multiple organs and the partitioning of energy between these organs, a suitable strategy can be devised for the treatment of chronic obesity.

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Section: Experimental Paradigms To Study Lipotoxicitymentioning

confidence: 99%

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

2004

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“…This response is also recognized as promotion of obesity‐linked inflammatory diseases including insulin resistance, nonalcoholic fatty liver disease (NAFLD), and atherosclerosis (Sethi & Hotamisligil, 1999). Obesity increases levels of inflammatory adipokines such as interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α), which induce insulin resistance (Sethi & Hotamisligil, 1999; Fasshauer et al ., 2003). IL‐6 is elevated by high insulin levels and leads to an increase of TNF‐α in plasma and white adipose tissue, which negatively impacts insulin signaling by inducing serine phosphorylation of the insulin receptor substrate‐1 (IRS‐1).…”

Section: Introductionmentioning

confidence: 99%

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

Hill

Fang

Miquet³

et al. 2016

Aging Cell

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SummaryGrowth hormone (GH) signaling stimulates the production of IGF‐1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high‐fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet‐induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD.

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“…13 -15 TNF-a has been attributed an important position in the pathogenesis of insulin resistance. 16,17 The actions of TNF-a are mediated by two distinct receptors, TNF receptors 1 and 2 (TNFR-I and TNFR-II). 18 There are soluble forms of both receptors, and TNF-a as well as both receptors are released from adipose tissue.…”

Section: Introductionmentioning

confidence: 99%

Testosterone and diurnal rhythmicity of leptin, TNF-α and TNF-II receptor in insulin-resistant myotonic dystrophy patients

et al. 2002

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OBJECTIVE:To investigate the leptin and TNF systems in relation to testosterone in insulin resistant myotonic dystrophy (DM1) subjects. DESIGN AND SUBJECTS: Fasting morning samples and diurnal sampling during 24 h. Forty-two DM1 subjects (20 women and 22 men; age 41.5 (28.5 -58.7) y, body mass index (BMI) 23.3 (18.6 -29.2) kg=m 2 ; median and 10th and 90th percentile, respectively). Fifty healthy volunteers (23 women and 27 men; age 42 (27.0 -56.9) y, BMI 24.0 (20.7 -29.7) kg=m 2 ). Nine men with DM1 and nine healthy men participated in diurnal sampling. MEASUREMENTS: Body composition was measured by bioelectric impedance analysis. Circulating levels of leptin, TNF-a, TNFR-II, insulin, testosterone and lipids were measured. The number of CTG triplet repeats was analysed. RESULTS: Basal as well as median 24 h levels of leptin and TNFR-II were significantly increased in DM1 patients, independent of body fat mass. This was associated with higher insulin and lower testosterone levels in DM1 patients. The genetic defect was related to leptin and TNFR-II levels in DM1 patients. CONCLUSION: Hyperleptinemia in DM1 is clearly linked to the concomitant hypogonadism. The genetic defect may directly or indirectly contribute to increased leptin levels. Increased exposure of cytokines may contribute to insulin resistance and other hormonal disturbances in DM1.

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The role of TNFα in adipocyte metabolism

Cited by 388 publications

References 0 publications

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation

Long‐lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high‐fat diet on metabolic function and energy expenditure

Testosterone and diurnal rhythmicity of leptin, TNF-α and TNF-II receptor in insulin-resistant myotonic dystrophy patients

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