Insulin attenuates the stimulatory effects of tumor necrosis factor α on 11β-hydroxysteroid dehydrogenase 1 in human adipose stromal cells

Handoko, K.; Yang, Kaiping; Strutt, Brenda; Khalil, Wahid; Killinger, D.W.

doi:10.1016/s0960-0760(00)00029-7

Cited by 38 publications

(24 citation statements)

References 25 publications

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“…Interestingly, 11␤-HSD1 activity decreased with increasing body mass index in the controls but not in patients with NAFLD. Thus, although there is strong evidence that TNF-␣ upregulates 11␤-HSD1 in vitro (18,24,55) and in transgenic animals overexpressing TNF-␣ (present study), its relevance in the pathogenesis of complex disease states in humans, such as the metabolic syndrome or NAFLD, awaits clarification. This will be a difficult task since 11␤-HSD1 activity may depend on 1) the time point during the development of the disease state and 2) the host of factors proposed to modulate 11␤-HSD1 activity (40,53), which may change continuously in these patients.…”

Section: Discussionmentioning

confidence: 78%

“…We have previously demonstrated that 11␤-HSD1 reductase is selectively upregulated by TNF-␣ in rat mesangial cells, enhancing the cortisone/ cortisol shuttle (18). Other studies have confirmed these data (16,24,55). TNF-␣ levels in serum, white adipose tissue, and liver were increased in obesity (25), type 2 diabetes mellitus (52), and nonalcoholic fatty liver disease (NAFLD) (26).…”

mentioning

confidence: 75%

“…cultures from rodents and humans (18,24,55). This topic is of biological and potentially clinical relevance because 1) that an array of results derived from animal studies indicates that an increased activity of hepatic 11␤-HSD1 increases fat deposits in the liver and insulin resistance and 2) that TNF-␣ levels, NAFLD, and insulin resistance appear to be interrelated in humans (2, 36) (see also INTRODUCTION).…”

Section: Discussionmentioning

confidence: 99%

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Tumor necrosis factor-α upregulates 11β-hydroxysteroid dehydrogenase type 1 expression by CCAAT/enhancer binding protein-β in HepG2 cells

Ignatova¹,

Kostadinova²,

Goldring³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive to active glucocorticoids. 11β-HSD1 plays a crucial role in the pathogenesis of obesity and controls glucocorticoid actions in inflammation. Several studies have demonstrated that TNF-α increases 11β-HSD1 mRNA and activity in various cell models. Here, we demonstrate that mRNA and activity of 11β-HSD1 is increased in liver tissue from transgenic mice overexpressing TNF-α, indicating that this effect also occurs in vivo. To dissect the molecular mechanism of this increase, we investigated basal and TNF-α-induced transcription of the 11β-HSD1 gene ( HSD11B1) in HepG2 cells. We found that TNF-α acts via p38 MAPK pathway. Transient transfections with variable lengths of human HSD11B1 promoter revealed highest activity with or without TNF-α in the proximal promoter region (−180 to +74). Cotransfection with human CCAAT/enhancer binding protein-α (C/EBPα) and C/EBPβ-LAP expression vectors activated the HSD11B1 promoter with the strongest effect within the same region. Gel shift and RNA interference assays revealed the involvement of mainly C/EBPα, but also C/EBPβ, in basal and only of C/EBPβ in the TNF-α-induced HSD11B1 expression. Chromatin immunoprecipitation assay confirmed in vivo the increased abundance of C/EBPβ on the proximal HSD11B1 promoter upon TNF-α treatment. In conclusion, C/EBPα and C/EBPβ control basal transcription, and TNF-α upregulates 11β-HSD1, most likely by p38 MAPK-mediated increased binding of C/EBPβ to the human HSD11B1 promoter. To our knowledge, this is the first study showing involvement of p38 MAPK in the TNF-α-mediated 11β-HSD1 regulation, and that TNF-α stimulates enzyme activity in vivo.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

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Tumor necrosis factor-α upregulates 11β-hydroxysteroid dehydrogenase type 1 expression by CCAAT/enhancer binding protein-β in HepG2 cells

Ignatova¹,

Kostadinova²,

Goldring³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…As a consequence, it could be suggested that the accentuation of 11␤-HSD-1 overexpression found in MAT of PHF animals is a counterregulatory phenomenon subsequent to the local microinflammatory syndrome induced by high-fat diet (42). It is established that in human adipose tissue, TNF-␣ and FFAs, which are natural ligands of PPAR␥, stimulate 11␤-HSD-1 activity through a modulation of 11␤-HSD-1 gene transcription (43,44). Because, in addition to MAT GR mRNA, MAT TNF-␣ mRNA and circulating FFA concentrations were increased in programmed rats fed with high-fat diet, the hypothesis above could explain, at least in part, the concomitant increase in MAT 11␤-HSD-1 mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

Postnatal Programming of Glucocorticoid Metabolism in Rats Modulates High-Fat Diet–Induced Regulation of Visceral Adipose Tissue Glucocorticoid Exposure and Sensitivity and Adiponectin and Proinflammatory Adipokines Gene Expression in Adulthood

et al. 2008

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OBJECTIVE-Alterations of the perinatal environment, which lead to increased prevalence of the metabolic syndrome in adulthood, program an upregulation of systemic and/or adipose tissue glucocorticoid metabolism (11␤-hydroxysteroid dehydrogenase type 1 [11␤-HSD-1]-induced corticosterone reactivation). We hypothesized that postnatal programming could modulate high-fat diet-induced adipose tissue dysregulation in adulthood. RESEARCH DESIGN AND METHODS-We compared the effects of chronic (since weaning) high-or low-fat diet in postnatally normofed (control) or overfed (programmed) rats. RESULTS-Postnatal programming accentuated high-fat dietinduced overweight, insulin resistance, glucose intolerance, and decrease in circulating and epididymal adipose tissue adiponectin. Neither manipulation altered liver function. Postnatal programming or high-fat diet increased systemic corticosterone production, which was not further modified when both manipulations were associated. Postnatal programming suppressed high-fat diet-induced decrease in mesenteric adipose tissue (MAT) glucocorticoid sensitivity and triggered high-fat dietinduced increase in MAT glucocorticoid exposure, subsequent to enhanced MAT 11␤-HSD-1 gene expression. MAT tumor necrosis factor (TNF)-␣, TNF-receptor 1, interleukin (IL)-6, resistin, and plasminogen activator inhibitor-1 mRNAs were not changed by high-fat feeding in control rats and showed a large increase in programmed animals, with this effect further enhanced by highfat diet for TNF-␣ and IL-6. CONCLUSIONS-Our data show for the first time that postnatal manipulation programs high-fat diet-induced upregulation of MAT glucocorticoid exposure, sensitivity, and inflammatory status and therefore reveal the pivotal role of the environment during the perinatal period on the development of diet-induced adipose tissue dysregulation in adulthood. They also urge the need for clinical trials with specific 11␤-HSD-1 inhibitors. Diabetes 57:669-677, 2008

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“…In contrast, the glucocorticoid-activating enzyme 11␤-HSD1 is enhanced by the proinflammatory cytokines TNF-␣, IL-1␤, and IL-6 (26,33,45,46,64,71,141). Chronically elevated 11␤-HSD1 activity has been associated with various adverse metabolic effects (7,142).…”

Section: Potential Role Of Impaired Corticosteroid Regulation In Westmentioning

confidence: 99%

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

Odermatt

2011

American Journal of Physiology-Renal Physiology

213

128

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The Western-style diet is characterized by its highly processed and refined foods and high contents of sugars, salt, and fat and protein from red meat. It has been recognized as the major contributor to metabolic disturbances and the development of obesity-related diseases including type 2 diabetes, hypertension, and cardiovascular disease. Also, the Western-style diet has been associated with an increased incidence of chronic kidney disease (CKD). A combination of dietary factors contributes to the impairment of renal vascularization, steatosis and inflammation, hypertension, and impaired renal hormonal regulation. This review addresses recent progress in the understanding of the association of the Western-style diet with the induction of dyslipidemia, oxidative stress, inflammation, and disturbances of corticosteroid regulation in the development of CKD. Future research needs to distinguish between acute and chronic effects of diets with high contents of sugars, salt, and fat and protein from red meat, and to uncover the contribution of each component. Improved therapeutic interventions should consider potentially altered drug metabolism and pharmacokinetics and be combined with lifestyle changes. A clinical assessment of the long-term risks of whole-body disturbances is strongly recommended to reduce metabolic complications and cardiovascular risk in kidney donors and patients with CKD.

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Insulin attenuates the stimulatory effects of tumor necrosis factor α on 11β-hydroxysteroid dehydrogenase 1 in human adipose stromal cells

Cited by 38 publications

References 25 publications

Tumor necrosis factor-α upregulates 11β-hydroxysteroid dehydrogenase type 1 expression by CCAAT/enhancer binding protein-β in HepG2 cells

Tumor necrosis factor-α upregulates 11β-hydroxysteroid dehydrogenase type 1 expression by CCAAT/enhancer binding protein-β in HepG2 cells

Postnatal Programming of Glucocorticoid Metabolism in Rats Modulates High-Fat Diet–Induced Regulation of Visceral Adipose Tissue Glucocorticoid Exposure and Sensitivity and Adiponectin and Proinflammatory Adipokines Gene Expression in Adulthood

The Western-style diet: a major risk factor for impaired kidney function and chronic kidney disease

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