Reduced Insulin-Like Growth Factor-I Serum Levels in Formerly Obese Women Subjected to Laparoscopic-Adjustable Gastric Banding or Diet-Induced Long-term Caloric Restriction

Mitterberger, Michael; Mattesich, Monika; Klaver, Elise; Piza‐Katzer, Hildegunde; Zwerschke, Werner

doi:10.1093/gerona/glr149

Cited by 9 publications

(9 citation statements)

References 66 publications

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“…Thus, the observed decrease in serum IGF1 could reflect an increase in growth hormone secretion. However, we did not detect a change in growth hormone levels with treatment, a finding consistent with the lack of an effect of caloric restriction on growth hormone levels reported in obese subjects in some human studies (Mitterberger et al 2011; Rasmussen et al 1995). …”

Section: Discussionsupporting

confidence: 91%

“…In turn, IGF1 modifies growth hormone secretion through a negative-feedback loop (Clemmons 2007). Increased IGF1 levels and decreased growth hormone secretion are associated with obesity (Garten, et al 2012), whereas decreased IGF1 levels are associated with caloric restriction (Mitterberger, et al 2011; Rasmussen, et al 1995). Thus, the observed decrease in serum IGF1 could reflect an increase in growth hormone secretion.…”

Section: Discussionmentioning

confidence: 99%

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Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

Turner

Dube

Branscum

et al. 2015

Journal of Endocrinology

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Excessive weight gain in adults is associated with a variety of negative health outcomes. Unfortunately, dieting, exercise, and pharmacological interventions have had limited long-term success in weight control and can result in detrimental side effects, including accelerating age-related cancellous bone loss. We investigated the efficacy of using hypothalamic leptin gene therapy as an alternative method for reducing weight in skeletally-mature (9-month-old) female rats and determined the impact of leptin-induced weight loss on bone mass, density, and microarchitecture, and serum biomarkers of bone turnover (CTx and osteocalcin). Rats were implanted with cannulae in the 3rd ventricle of the hypothalamus and injected with either recombinant adeno-associated virus encoding the gene for rat leptin (rAAV-Leptin, n=7) or a control vector encoding green fluorescent protein (rAAV-GFP, n=10) and sacrificed 18 weeks later. A baseline control group (n=7) was sacrificed at vector administration. rAAV-Leptin-treated rats lost weight (−4±2%) while rAAV-GFP-treated rats gained weight (14±2%) during the study. At study termination, rAAV-Leptin-treated rats weighed 17% less than rAAV-GFP-treated rats and had lower abdominal white adipose tissue weight (−80%), serum leptin (−77%), and serum IGF1 (−34%). Cancellous bone volume fraction in distal femur metaphysis and epiphysis, and in lumbar vertebra tended to be lower (p<0.1) in rAAV-GFP-treated rats (13.5-months-old) compared to baseline control rats (9-months-old). Significant differences in cancellous bone or biomarkers of bone turnover were not detected between rAAV-Leptin and rAAV-GFP rats. In summary, rAAV-Leptin-treated rats maintained a lower body weight compared to baseline and rAAV-GFP-treated rats with minimal effects on bone mass, density, microarchitecture, or biochemical markers of bone turnover.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

Turner

Dube

Branscum

et al. 2015

Journal of Endocrinology

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“…Human sWAT samples were taken from persons undergoing routine abdominoplasty at the Institute for Plastic and Reconstructive Surgery (Medical University Innsbruck) ( Mitterberger et al, 2010 , Mitterberger et al, 2011 , Mitterberger et al, 2012 , Mitterberger et al, 2014a , Mitterberger et al, 2014b ). The patients gave their informed written consent and had been approved by the ethical committee of Innsbruck Medical University, Austria, according to the Declaration of Helsinki.…”

Section: Methodsmentioning

confidence: 99%

Weight Loss Upregulates the Small GTPase DIRAS3 in Human White Adipose Progenitor Cells, Which Negatively Regulates Adipogenesis and Activates Autophagy via Akt–mTOR Inhibition

et al. 2016

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Long-term weight-loss (WL) interventions reduce insulin serum levels, protect from obesity, and postpone age-associated diseases. The impact of long-term WL on adipose-derived stromal/progenitor cells (ASCs) is unknown. We identified DIRAS3 and IGF-1 as long-term WL target genes up-regulated in ASCs in subcutaneous white adipose tissue of formerly obese donors (WLDs). We show that DIRAS3 negatively regulates Akt, mTOR and ERK1/2 signaling in ASCs undergoing adipogenesis and acts as a negative regulator of this pathway and an activator of autophagy. Studying the IGF-1–DIRAS3 interaction in ASCs of WLDs, we demonstrate that IGF-1, although strongly up-regulated in these cells, hardly activates Akt, while ERK1/2 and S6K1 phosphorylation is activated by IGF-1. Overexpression of DIRAS3 in WLD ASCs completely inhibits Akt phosphorylation also in the presence of IGF-1. Phosphorylation of ERK1/2 and S6K1 is lesser reduced under these conditions. In conclusion, our key findings are that DIRAS3 down-regulates Akt–mTOR signaling in ASCs of WLDs. Moreover, DIRAS3 inhibits adipogenesis and activates autophagy in these cells.

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“…These are more consistent in showing a reduction in levels in response to a variety of approaches, namely, caloric restriction [45], gastric banding [87], physical activity [88], and a combination of dietary restriction and exercise training [89]. Whilst these findings are interesting, measurement of IGF-I in the context of obesity is currently confined to research studies.…”

Section: The Role Of Igf Axis Proteins In Managing Malnutrition Anmentioning

confidence: 96%

The Insulin-Like Growth Factor System and Nutritional Assessment

Livingstone

2012

Scientifica

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Over recent years there has been considerable interest in the role of the insulin-like growth factor (IGF) system in health and disease. It has long been known to be dysregulated in states of under- and overnutrition, serum IGF-I levels falling in malnourished patients and responding promptly to nutritional support. More recently, other proteins in this system have been observed to be dysregulated in both malnutrition and obesity. Currently no biochemical marker is sufficiently specific for use in screening for malnutrition, but levels may be valuable in providing information on nutritional status and in monitoring of nutritional support. All have limitations as nutritional markers in that their serum levels are influenced by factors other than nutritional status, most importantly the acute phase response (APR). Levels should be interpreted along with clinical findings and the results of other investigations such as C-reactive protein (CRP). This paper reviews data supporting the use of proteins of the IGF system as nutritional markers.

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Reduced Insulin-Like Growth Factor-I Serum Levels in Formerly Obese Women Subjected to Laparoscopic-Adjustable Gastric Banding or Diet-Induced Long-term Caloric Restriction

Cited by 9 publications

References 66 publications

Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

Hypothalamic leptin gene therapy reduces body weight without accelerating age-related bone loss

Weight Loss Upregulates the Small GTPase DIRAS3 in Human White Adipose Progenitor Cells, Which Negatively Regulates Adipogenesis and Activates Autophagy via Akt–mTOR Inhibition

The Insulin-Like Growth Factor System and Nutritional Assessment

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