Growth Hormone and Adipocyte Function in Obesity

Nam, Su Youn; Marcus, Claude

doi:10.1159/000053211

Cited by 62 publications

(50 citation statements)

References 120 publications

(193 reference statements)

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“…Given that GH secretion is recovered after significant weight loss, it is thought that impaired GH secretion is a consequence of obesity (Rasmussen et al 1995, Nam & Marcus 2000. Recent data, however, demonstrate the rapid suppression of GH secretion relative to excess calorie consumption (Cornford et al 2011(Cornford et al , 2012.…”

Section: Discussionmentioning

confidence: 99%

Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain

Steyn

Xie

Huang

et al. 2013

Journal of Endocrinology

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Pathological changes associated with obesity are thought to contribute to GH deficiency. However, recent observations suggest that impaired GH secretion relative to excess calorie consumption contributes to progressive weight gain and thus may contribute to the development of obesity. To clarify this association between adiposity and GH secretion, we investigated the relationship between pulsatile GH secretion and body weight; epididymal fat mass; and circulating levels of leptin, insulin, non-esterified free fatty acids (NEFAs), and glucose. Data were obtained from male mice maintained on a standard or high-fat diet. We confirm the suppression of pulsatile GH secretion following dietary-induced weight gain. Correlation analyses reveal an inverse relationship between measures of pulsatile GH secretion, body weight, and epididymal fat mass. Moreover, we demonstrate an inverse relationship between measures of pulsatile GH secretion and circulating levels of leptin and insulin. The secretion of GH did not change relative to circulating levels of NEFAs or glucose. We conclude that impaired pulsatile GH secretion in the mouse occurs alongside progressive weight gain and thus precedes the development of obesity. Moreover, data illustrate key interactions between GH secretion and circulating levels of insulin and reflect the potential physiological role of GH in modulation of insulin-induced lipogenesis throughout positive energy balance. Key Words" pulsatile GH secretion " dietary-induced weight gain " insulin " non-esterified free fatty acids " adiposity

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Section: Discussionmentioning

confidence: 99%

Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain

Steyn

Xie

Huang

et al. 2013

Journal of Endocrinology

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“…This conflicting result of GH action may come from the different characteristics between cell lines and primary preadipocytes. Actually, it was pointed out that primary preadipocytes may have been at a later stage of adipogenesis beyond that of established preadipocyte models (Wabitsch et al 1995, Gregoire et al 1998, Nam & Marcus 2000. Alternatively, treatment with GH is not required in primary cultures due to their prior in vivo exposure to circulating GH.…”

Section: Discussionmentioning

confidence: 99%

Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARγ pathway

Kawai¹,

Namba²,

Mushiake³

et al. 2007

Journal of Molecular Endocrinology

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Growth hormone-deficient (GHD) patients show a decreased number of adipocytes, which is normalized by GH replacement, indicating an adipogenic effect of GH. However, the precise mechanisms underlying this effect remain to be clarified. In this study, we investigated the adipogenic effect of GH. GH stimulated MDI (3-isobutyl-1-methylxanthine, dexamethasone, and insulin)-induced adipogenesis of 3T3-L1 cells with early induction of peroxisome proliferator-activated receptors (PPAR)g2 expression. This adipogenic effect of GH was suppressed by overexpression of Stat5A mutant (Stat5A-Y694F), a transcriptional suppressor for the GH-Stat5A/5B signaling pathway, with the reduction of PPARg2 expression. Next, we investigated the relationship between Stat5A/5B and CCAAT/enhancer binding protein (C/EBP)b/d or PPARg in 3T3-L1 cells. Stat5A/5B stimulated C/EBPb-and C/EBPd-induced adipogenesis with enhancement of PPARg2 expression. In addition, Stat5A/5B enhanced the transcriptional activity of C/EBPb/d in the PPARg gene promoter. Furthermore, Stat5A/5B stimulated PPARg-induced adipogenesis and enhanced the transcriptional activity of PPARg. These results suggest that the GH-Stat5A/5B signaling pathway stimulates adipogenesis in cooperation with C/EBPb/d and PPARg. To completely understand the effect of GH, cDNA microarray analysis was performed to screen genes affected by GH during MDI-induced adipogenesis. Among 4277 genes, 18 and 19 genes were up-and down-regulated respectively. cDNA microarray analysis also indicated the up-regulation of PPARg and the modulation of expression of genes coding for growth factors or growth factor receptors, suggesting that GH stimulates adipogenesis in association with the modulation of cell growth. Thus, the GHStat5A/B signaling pathway stimulates adipogenesis through two distinct steps. In addition, cDNA microarray data provide us the further insights underlying the adipogenic effect of GH.

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“…Nevertheless, IGF-1 serum levels decreased in adult OF mini-pigs, whereas TG and glucose remained stable and low. The transcription of IGF-1 in a tissue can reflect the level of IGF-1 protein synthesis 53 and, as in the case of interleukins, 54 IGF-1 has an autocrine-paracrine action. 55,56 IGF-1 57 In obese animals, this relationship may be sufficient to maintain low TG and glucose plasma concentrations without hyperinsulinism.…”

Section: Discussionmentioning

confidence: 99%

Childhood obesity and insulin resistance in a Yucatan mini-piglet model: putative roles of IGF-1 and muscle PPARs in adipose tissue activity and development

et al. 2005

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OBJECTIVE:To explore metabolic and cellular modifications induced during childhood obesity, in a novel animal model of obese mini-piglets. DESIGN: A total of 10 four-month old Yucatan mini-pigs were followed from prepuberty to adulthood. Animals were divided into two groups. The first one had been overfed (OF) a western-type diet and the second one had been normally fed a control recommended human-type diet (NF). MEASUREMENTS: Plasma insulin-like growth factor 1 (IGF-1), insulin, leptin, nonesterified fatty acids, triglycerides (TGs) and glucose were determined at sexual maturity and at young adulthood. Quantitative gene expressions of peroxysome-proliferatoractivated receptors (PPARs), glucose transporter 4, insulin receptor, IGF-1, leptin and interleukin-6 (IL-6) in skeletal muscle, adipose tissue and liver were also measured at both stages. Adult insulin sensitivity was measured via euglycaemichyperinsulinaemic clamps. RESULTS: Increased body weight in adult OF pigs was associated with increased body size and low insulin sensitivity. Sexually mature OF pigs had higher IGF-1 plasma concentrations than their lean littermates (Po0.05). In the OF group, TGs and glucose were both decreased (Po0.05). Muscle PPARg and a in OF pubescent pigs as compared to NF pigs were 11 times higher and 20 times lower, respectively (Po0.01). CONCLUSION: Obesity and insulin resistance induced by overfeeding mini-pigs during development and puberty were not associated with the cluster of metabolic modifications frequently observed in their adult littermates. Increased IGF-1 concentrations and modifications of skeletal muscle PPAR (a and g) expressions may help the young obese pig to partially regulate its glycaemia and triglyceridaemia through an increase of fat mass, which maintains its high insulin sensitivity.

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Growth Hormone and Adipocyte Function in Obesity

Cited by 62 publications

References 120 publications

Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain

Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain

Growth hormone stimulates adipogenesis of 3T3-L1 cells through activation of the Stat5A/5B-PPARγ pathway

Childhood obesity and insulin resistance in a Yucatan mini-piglet model: putative roles of IGF-1 and muscle PPARs in adipose tissue activity and development

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