Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance.

Hofmann, Cecilia; Lorenz, Kathryn; Braithwaite, Susan S.; Colca, Jerry R.; Palazuk, Barbara J.; Hotamışlıgil, Gökhan S.; Spiegelman, Bruce M.

doi:10.1210/endo.134.1.8275942

Cited by 307 publications

(171 citation statements)

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“…The cytokine is overexpressed in adipose tissues from genetically obese rodents (41,54,55) and in human obesity (56,57). The causal relationship between TNF-␣ and insulin resistance has been demonstrated in vivo by TNF-␣ neutralization that increases insulin sensitivity in the obese insulin-resistant Zucker fa/fa rat (41).…”

Section: Table IV Effect Of Tnf-␣ Treatment On the Lipolytic Activitymentioning

confidence: 99%

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Hadri

Courtalon

Gauthereau

et al. 1997

Journal of Biological Chemistry

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Modulation of ␤-adrenoreceptor expression by tumor necrosis factor-␣ (TNF-␣) was investigated in murine 3T3-F442A adipocytes. TNF-␣ treatment of mature adipocytes decreased ␤ 3 -adrenoreceptor mRNA content in a time-and concentration-dependent manner, with a 8.5-fold decrease observed after a 6-h exposure to 300 pM TNF-␣. ␤ 1 -Adrenoreceptor mRNA abundance was slightly decreased by TNF-␣ treatment, while ␤ 2 -adrenoreceptor mRNA levels were potently induced (6-fold increase at 6 h). (؊)-[ 125 I]Iodocyanopindolol saturation and competition binding experiments indicated that TNF-␣ induced a 2-fold decrease in ␤ 3 -adrenoreceptor number, a nonsignificant reduction in ␤ 1 -subtype population, and a ϳ4.5-fold increase in ␤ 2 -adrenoreceptor density. This correlated with a lower EC 50 value measured for epinephrine in stimulating adenylyl cyclase, whereas the EC 50 value for norepinephrine increased. Nuclear run-on assays on isolated nuclei and mRNA stability measurements showed that TNF-␣ increased both ␤ 2 -adrenoreceptor gene transcription and ␤ 2 -adrenoreceptor mRNA half-life, while ␤ 1 -and ␤ 3 -adrenoreceptor gene expression was modulated only at the transcriptional level by the cytokine. These findings demonstrate a differential modulation by TNF-␣ of the three ␤-adrenoreceptor subtypes in adipocytes, which may contribute to metabolic disorders induced by the cytokine in the adipocyte.Tumor necrosis factor-␣ (TNF-␣) 1 is a multifunctional cytokine that was originally identified as a tumoricidal protein (1). Subsequent investigations have shown that TNF-␣ was fundamentally involved in control of the growth, differentiation, and metabolism in several normal cells and tissues.A sum of work has been focused on the role of TNF-␣ in the regulation of adipocyte development and metabolism (1, 2). Thus, TNF-␣ strongly inhibits adipose conversion and even causes a dramatic dedifferentiation of adipocytes in culture (3-6). Moreover, it is also documented that TNF-␣ decreases the synthesis and activity of several proteins essential for lipogenesis and triglyceride accumulation in adipocytes. These include lipoprotein lipase (5, 7-9), acetyl-coenzyme A carboxylase (4, 10, 11), acyl-coenzyme A synthetase (12), stearoyl-coenzyme A desaturase (12), and the insulin-sensitive glucose transporter GLUT4 (13,14).In addition to the above effects on adipogenesis and reduction of de novo fatty acid synthesis, TNF-␣ also depletes triglycerides from adipocytes by directly increasing lipolysis (15-17). So far, the molecular mechanism by which the cytokine potentiates lipolysis remains unclear (17).Through activation of three ␤-AR subtypes, catecholamines exert a key role in the regulation of lipid metabolism in adipocytes. They modulate cAMP-dependent processes such as lipolysis and the genetic control of the lipogenic and thermogenic pathways. As regards the pleiotropic effects of TNF-␣ on several metabolic pathways in adipocytes, and to the key role of the ␤-AR system in lipid mobilization, it is possible that an interplay between TNF...

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Section: Table IV Effect Of Tnf-␣ Treatment On the Lipolytic Activitymentioning

confidence: 99%

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Hadri

Courtalon

Gauthereau

et al. 1997

Journal of Biological Chemistry

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“…TNF-alpha (TNFa) from adipose tissue may play a major role in stimulating the insulin resistance [22][23][24][25] .…”

Section: Tumor Necrosis Factor-alphamentioning

confidence: 99%

Relation between Type 2 Diabetes and obesity: A review

Kumar¹

2013

Int Jour of Biomed Res

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“…For example, troglitazone reversed the TNF-induced impairment in insulin-stimulated glucose disposal and partially reversed the hyperlipidemia, but had no effect on the increase in insulin levels or on insulin receptor tyrosine kinase activity (119). Interestingly, pioglitazone is able to partially reverse the overexpression of TNF and its receptors seen in muscle and fat from diabetic mice (120).…”

Section: Insulin Resistance and Longevity: Beyond Glucosementioning

confidence: 99%

Endocrine and metabolic changes in human aging

Banks

Morley

2000

AGE

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"Aging and death are inevitable. We have no desire to prolong life, if such prolongation entails only added days and years of misery and suffering. On the other hand, for the first time in history, man has within his grasp potent medications of many kinds, among the more important of which are specific hormones capable of retarding if not stopping some of the undesirable features of growing old". Thomas Hodge McGavack Geriatrics 18:181-191 (1963) ABSTRACT Numerous alterations in hormonal secretion occur with aging. In general, these tend towards a disintegration of the normal cyclic secretory patterns resulting in lower total circulating levels. In addition, declines in receptors and postreceptor function further decreases the ability of the hormonal orchestra to maintain coordinated function throughout the organism. Clues to some of these agerelated changes in humans may come from the study of simpler organisms where regulatory systems are known to modulate the aging process. In particular, the interactions among the environment, hormones, and insulin receptor genes have led to new insights into the genetic control of longevity and the development of syndrome X.It is now well established, as summarized in Table 1, that the levels of many hormones are altered with aging (1). Some hormonal levels decrease, reflecting endocrine gland failure, whereas others increase, often because of end organ failure due to a decrease in receptors or a failure of postreceptor function. In the last decade, it has become popular to look to hormone replacement therapy as a mechanism to reverse the aging process. It has become popular to consider this the "hormonal fountain of youth". With aging, dysregulation of food intake accompanied by sarcopenia ('wasting of the flesh") occurs (2). A number of hormonal mechanisms are related to the physiological anorexia of aging (3). In particular, recent studies have suggested that alterations in circulating testosterone levels lead in males to increased leptin levels and thus to anorexia (4).Another area of intense interest in understanding the mechanisms of aging in humans has been the alterations that occur in glucose metabolism with aging and the role of age-related glucose end products (AGE) in accelerating the aging process (5). This area has been closely linked with the changes in nutrition that occur with aging, with insulin resistance, and more recently, with the genes that encode for the insulin receptor. It is of interest that the hormonal changes produced by dietary restriction in rodents are similar to the agerelated hormonal changes in humans, as shown in Table 2 (6). This raises the possibility that these hormonal changes are protective, i,e. slow down metabolism and thus slow down the aging process. This creates a "chicken or egg" hypothesis, illustrated in Figure 1, which asks the question: do aging changes occur because of the decline in hormones or do high hormone levels produce aging changes?This review will briefly examine the available data in each of these areas and...

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Altered gene expression for tumor necrosis factor-alpha and its receptors during drug and dietary modulation of insulin resistance.

Cited by 307 publications

References 0 publications

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Differential Regulation by Tumor Necrosis Factor-α of β1-, β2-, and β3-Adrenoreceptor Gene Expression in 3T3-F442A Adipocytes

Relation between Type 2 Diabetes and obesity: A review

Endocrine and metabolic changes in human aging

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