The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice

Hamrick, Mark W.; Dukes, Amy; Arounleut, Phonepasong; Davis, Catherine L.; Periyasamy‐Thandavan, Sudharsan; Mork, Sarah; Herberg, Samuel; Johnson, Maribeth H.; Isales, Carlos M.; Hill, William; Ötvös, László; Chantemèle, Eric J. Belin de

doi:10.1016/j.exger.2015.07.014

Cited by 23 publications

(16 citation statements)

References 26 publications

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“…Similar findings were revealed by another report that observed higher circulating concentrations of leptin and IGF-1 in excess abdominal fat [13]. In the experimental animals (mice) administration of recombinant leptin induced a three-fold increase in liver-derived IGF-1 [7]. Moreover, an in vitro study showed that the addition of leptin increased the expression of IGF-1 in MDA-MB-361 and SK-BR-3 breast cancer cell-lines [14].…”

Section: Introductionsupporting

confidence: 86%

“…Leptin is closely linked with several growth factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor 21 (FGF21), and insulin-like growth factor-1 (IGF-1) [5], [6], [7] (Table 1) [1], [4], [8], [9], [10], [11]. A study on human subjects detected an increased gene expression of leptin and IGF-1 in the subcutaneous fat of the obese group, while the expression of IGF-1 in the visceral fat was higher in the control group (non-obese cholecystectomy cases) [12].…”

Section: Introductionmentioning

confidence: 99%

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Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Ray

2017

Hormone Molecular Biology and Clinical Investigation

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Abstract:Obesity is associated with the risk of several health disorders including certain cancers. Among obesity-related cancers, postmenopausal breast carcinoma is a well-studied one. Apart from an increase in certain types of lipids in obesity, excess adipose tissue releases many hormone-like cytokines/adipokines, which are usually pro-inflammatory in nature. Leptin is one of such adipokines and significantly linked with the intracellular signaling pathways of other growth factors such as insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2). In general, HER2 is overexpressed in roughly 30% of breast carcinomas; its presence indicates aggressive tumor behavior. Conversely, HER2 has certain effects in normal conditions such as differentiation of preadipocytes, cardiovascular health and vitamin D metabolism. HER2 has no known endogenous ligand, but it may form dimers with other three members of the epidermal growth factor receptor (EGFR) family and can activate downstream signaling pathways. Furthermore, HER2 is intimately connected with several enzymes, e.g. fatty acid synthase (FASN), phosphatidylinositol 3-kinase (PI3K), AKT and mechanistic target of rapamycin (mTOR), all of which play significant regulatory roles in lipogenic pathways or lipid metabolism. In obesity-related carcinogenesis, characteristics like insulin resistance and elevated IGF-1 are commonly observed. Both IGF-1 and leptin can modulate EGFR and HER2 signaling pathways. Although clinical studies have shown mixed results, the behavior of HER2+ tumor cells including HER2 levels can be altered by several factors such as obesity, leptin and fatty acids. A precise knowledge is useful in new therapeutic approaches against HER+ tumors.

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Section: Introductionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Ray

2017

Hormone Molecular Biology and Clinical Investigation

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“…Leptin is an appetite-suppressive adipokine that links food intake with energy expenditure and body composition. 27 Leptin is known to increase muscle mass by decreasing the expression of atrophy-related factors such as myostatin, MuRF1, and muscle atrophy F-box in muscles, 28 possibly by regulating IGF1 levels, 29 although we found no significant correlation between serum leptin and IGF1 levels in our cohort ( Table 3). Changes in leptin sensitivity with ageing could contribute to the age-related degeneration of multiple organs, including skeletal muscles.…”

Section: Discussionmentioning

confidence: 57%

Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention

Shyh‐Chang

et al. 2019

J cachexia sarcopenia muscle

181

114

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Background Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing‐related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. Methods A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non‐sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty‐two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre‐intensive and post‐intensive lifestyle interventions, were measured. Results The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non‐sarcopenic subjects, serum interleukin (IL)‐6, IL‐18, tumour necrosis factor‐α (TNF‐α), TNF‐like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF‐α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6‐fold and 14.3‐fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4‐fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF‐α, IL‐18, insulin, and adiponectin (all P < 0.05). Conclusions High levels of the inflammatory cytokines TWEAK and TNF‐α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could signif...

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“…Leptin is mainly produced by adipocyte304647. Studies have also shown leptin production by other tissues, including skeletal muscle4849. Thus, we checked Leptin expression in Leptin- expressing tissues iWAT and Sk.M, and Ppar-γ expression in all the three tissues by normalized with the recommended gene pair, most and least stable gene, respectively (Fig.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of candidate reference genes for RT-qPCR studies in three metabolism related tissues of mice after caloric restriction

Gong

Sun

Chen

et al. 2016

Sci Rep

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Reverse transcription quantitative-polymerase chain reaction (RT-qPCR) is a routine method for gene expression analysis, and reliable results depend on proper normalization by stable reference genes. Caloric restriction (CR) is a robust lifestyle intervention to slow aging and delay onset of age-associated diseases via inducing global changes in gene expression. Reliable normalization of RT-qPCR data becomes crucial in CR studies. In this study, the expression stability of 12 candidate reference genes were evaluated in inguinal white adipose tissue (iWAT), skeletal muscle (Sk.M) and liver of CR mice by using three algorithms, geNorm, NormFinder, and Bestkeeper. Our results showed β2m, Ppia and Hmbs as the most stable genes in iWAT, Sk.M and liver, respectively. Moreover, two reference genes were sufficient to normalize RT-qPCR data in each tissue and the suitable pair of reference genes was β2m-Hprt in iWAT, Ppia-Gusb in Sk.M and Hmbs-β2m in liver. By contrast, the least stable gene in iWAT or Sk.M was Gapdh, and in liver was Pgk1. Furthermore, the expression of Leptin and Ppar-γ were profiled in these tissues to validate the selected reference genes. Our data provided a basis for gene expression analysis in future CR studies.

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The adipokine leptin mediates muscle- and liver-derived IGF-1 in aged mice

Cited by 23 publications

References 26 publications

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention

Evaluation of candidate reference genes for RT-qPCR studies in three metabolism related tissues of mice after caloric restriction

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