Abstract
Purpose
Obesity is a severe public health problem worldwide, leading to an insulin-resistant state in liver, adipose, and muscle tissue, representing a risk factor for type 2 diabetes mellitus, cardiovascular diseases, and cancer. We have shown that abdominal obesity is associated with homeostasis derangement, linked to several hormonal and paracrine factors. Data regarding potential link between GH/IGF1 axis, bone mineral density, and inflammation in obesity are lacking. Thus, aim of this study was to evaluate correlation among IGF-1, BMD, and inflammation in obese individuals.
Methods
The study included 426 obese subjects, mean age 44.8 ± 14 years; BMI 34.9 ± 6.1. Exclusion criteria were chronic medical conditions, use of medications affecting bone metabolism, hormonal and nutritional status, recent weight loss, and prior bariatric surgery. Patients underwent measurements of BMD and body composition by DEXA and were evaluated for hormonal, metabolic profile, and inflammatory markers.
Results
In this population, IGF-1 was inversely correlated with abdominal FM% (p < 0.001, r 2 = 0.12) and directly correlated with osteocalcin (OSCA) (p < 0.002, r 2 = 0.14). A negative correlation was demonstrated between IGF-1 levels and nonspecific inflammatory index, such as fibrinogen (p < 0.01, r 2 = 0.04) and erythrocyte sedimentation rate (p < 0.0001, r 2 = 0.03). IGF-1 was directly correlated with higher BMD, at both lumbar (p < 0.02, r 2 = 0.03) and femoral site (p < 0.04, r 2 = 0.03).
Conclusions
In conclusion, our results show that higher levels of serum IGF-1 in obese patients correlate with lower inflammatory pattern and better skeletal health, as demonstrated by higher BMD and osteocalcin levels. These results lead to speculate the existence of a bone-adipose-muscle interplay modulating energy homeostasis, glucose, bone metabolism, and chronic inflammation in individuals affected by abdominal obesity.
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Introduction
Obesity is a severe public health problem with an increasing prevalence and high impact on mortality and morbidity worldwide. Obesity leads to many adverse health consequences. In fact, it induces an insulin-resistant state in adipose tissue, liver, and muscle and represents a strong risk factor for the development of type 2 diabetes mellitus, cardiovascular diseases, and cancer [1].
The World Health Organization defines obesity as an abnormal or excessive fat accumulation that presents a risk to health, characterized by a body mass index (BMI) of ≥30 kg/m2. However, this definition, based on the BMI, does not consider the body composition of the subjects and the relative contributions of fat-free mass and fat mass to body weight and their implication in determining the chronic metabolic alterations induced by obesity. While it is well recognized the detrimental effect of abdominal adipose tissue on chronic metabolic alterations, less is known about the role of lean mass in obese subjects and the potential interactions between adipose and lean tissues. Since recent studies have demonstrated that obesity should not be considered only as an increase in body weight, it has become clear how it should be stressed the importance of body composition and the role that the various components of fat and lean mass might play in metabolic control, more than BMI itself.
Indeed, several hormonal and environmental factors can be involved in influencing body weight and fat accumulation and it is known that increased production of adipokines by visceral fat results in adverse effects on metabolic status, cardiovascular homeostasis, and skeletal health [2].
Moreover, obesity has been associated with sarcopenia, a condition characterized by progressive decline of muscle mass, quality, and strength likely due to the reduced physical activity over the time in obese individuals, leading to a new pathological condition defined as sarcopenic obesity [3].
Osteoporosis is a metabolic bone disease characterized by an increased risk of developing spontaneous or traumatic fracture due to skeletal fragility [4]. The relationship between fat and bone is a rapidly growing area in bone research, and a number of findings are relevant to the pathophysiology of increased bone fragility in obese individuals [5, 6].
In fact, a cross talk between fat, muscle, and bone has been speculated, and it might constitute a homeostatic feedback system in which adipokines, cytokines, hormones, and growth factors produced by adipose, muscle, and skeletal tissues represent the link of an active bone–muscle-adipose axis which probably represents a homeostatic system to maintain health.
Interestingly, the growth hormone (GH)/Insulin-like grow factor-1 (IGF-1) axis is involved in a large number of functions, from childhood to senescence, regulating growing, aging, and lifespan [7]. In particular, a declined function of GH/IGF-1 axis has been linked to age-related changes in body composition, metabolic functions, and to an increased risk of cardiovascular disease [8].
Thus, reduced GH levels emerge as a potential important biomarker of aging, and GH decline can accelerate aging processes and it might be associated with significant “costs” in terms of longevity.
Circulating levels of GH and IGF-1, the key mediator of the most GH actions, decline with age starting soon after sexual and physical maturation attempts [9].
In addition, the chronic low-grade inflammation associated with aging-related changes in fat distribution and function is considered, as well as the ‘inflammatory load’, related to the life-time history of infectious diseases, and has thought of being among the major determinants of human aging and lifespan [10, 11]. Increase of adipose tissue in obese humans and animals involves adipocyte hypertrophy as well as hyperplasia, which promote inflammation by changing the secretory cell profile, including production and secretion of proinflammatory adipokines as TNF-α and IL-6 [12, 13].
Thus, aim of this study was to evaluate the potential correlation among IGF-1, BMD, and inflammation status in adult subjects affected by obesity.
Materials and methods
Subjects
This cross-sectional study included 426 obese subjects (86 men and 340 female; mean age: 44.8 ± 14 years; BMI 34.9 ± 6.1 kg/m2), selected from a cohort of patients admitted to the day hospital of the Department of Experimental Medicine, Section of Medical Pathophysiology, Endocrinology and Nutrition, Policlinico Umberto I, Sapienza University of Rome, for clinical evaluation and treatment of obesity.
Exclusion criteria were: chronic medical conditions or use of medications affecting bone metabolism, hormonal, and nutritional status, 25-OH vitamin D (vitamin D) supplementation, recent weight loss, and prior bariatric surgery. All subjects provided informed consent before taking part in the study, and the local ethical committee approved the research protocol.
Patients underwent complete medical history and clinical examination. Blood samples were collected in the morning (07.00–08.00 am) after an overnight fast. Sera were then kept at −80 °C until analysis. Anthropometric measurements included weight and height; body weight was evaluated as the subjects were fasting overnight and wearing underwear. BMI was calculated as weight (kg)/height2 (m2). Patients underwent measurements of bone mineral density at lumbar and hip site (BMD g/cm2) and of body composition [lean mass (LM), total and trunk fat mass (TFM)] by dual X-ray absorptiometry (DEXA), and were evaluated for hormonal and metabolic profile and inflammatory markers.
Assays
Osteocalcin (OSCA) was measured with solid-phase commercial RIAs (provided by Diagnostic Products, Los Angeles, CA, and Diagnostics Systems Laboratories, Inc.Webster, TX). Measurements of glucose concentrations were assessed by the standard immuno-enzymatic methods, while insulin was measured by radioimmunoassay. IGF-1 was assayed by an immunoradiometric assay (Diagnostic System Laboratories Inc., Webster, TX, USA). Insulin levels were measured by radioimmunoassay, while fibrinogen levels were measured by an automated clinical chemistry analyzer (Modular P and Modular E for PSA, Roche Diagnostics GmbH, Mannheim, Germany). The intra- and inter-assay coefficients of variations for all hormonal assays ranged 3.4–6.2 and 3.6–8.4%, respectively. All measurements were performed in duplicate.
Dual-energy-X-ray absorptiometry measurement
Body fat mass, fat-free mass (kg), and both lumbar and femoral BMD were measured by DEXA (Dual-energy-X-ray absorptiometry, Hologic 4500 RDR), with coefficient of variation of <1% for bone density and <1.5% for fat mass. Amount of trunk fat mass was distinguished from peripheral and appendicular fat mass as a measure of abdominal adiposity. In particular, trunk fat was defined as the adipose tissue localized within the region below the chin, delineated by vertical lines within the left and right glenoid fossae bordering laterally to the ribs, and by the oblique lines that cross the femoral necks and converge below the pubic symphysis.
Statistical analysis
Data are depicted as the mean ± SD of absolute value except for skewed variables, which were instead presented as median (interquartile range 25–75%). Continuous variables were normally distributed (Shapiro–Wilk test) and were analyzed using Student’s t test for paired or unpaired data. Pearson’s 2 test, Wilcoxon’s signed-rank test, and Spearman’s correlation analysis as appropriate. Statistical analysis was performed using the computer statistical package SPSS/10.0 (SPSS, Chicago, IL, USA) and SAS/6.4 (SAS Institute Cary, NC, USA).
Results
A total of 426 obese subjects (86 men and 340 women), mean age 44.8 years, were included in the final analysis. Clinical and biochemical characteristics of this population have already been described elsewhere [14]. Briefly, BMI of the female population was 35.2 ± 5.2, while BMI of male population was 35.4 ± 6.1. As previously described [14], no differences were found between male and female gender in any of the parameters considered, as depicted in Table 1. Interestingly, in both female and male subjects, we found an inverse correlation between IGF-1 and fat mass (Fig. 1, p < 0.001, r 2 = 0.12), accordingly with the observation that higher levels of IGF-1 were directly associated with higher degree of lean mass, as we previously demonstrated elsewhere [14].
Moreover, a positive correlation between IGF-1 and the non-collagenic matrix protein osteocalcin, marker of bone formation (Fig. 2, p < 0.002, r 2 = 0.14), as well as an inverse correlation between IGF-1 and nonspecific inflammatory markers, such as fibrinogen (Fig. 3a, p < 0.009, r 2 = 0.04) and erythrocyte sedimentation rate (Fig. 3b, p < 0.0001, r 2 = 0.03), were found.
Finally, IGF-1, as expected being this factor anabolic for the bone, was directly correlated with higher BMD, at both lumbar (Fig. 4a, p < 0.02, r 2 = 0.03) and femoral site (Fig. 4b, p < 0.04, r 2 = 0.03). Proinflammatory cytokines were not significantly modified in this population of young obese subjects (dat not shown). Thus, no correlations were found among IGF-1, BMD, and fat issue (data not shown).
Discussion
The results presented in the manuscript demonstrate that higher levels of serum IGF-1 in adult obese patients are associated with a lower inflammatory pattern and that a direct association between both lumbar and femoral BMD is present for higher IGF-1 serum levels.
Aging correlates with increased risk of cancer, diabetes, atherosclerosis, metabolic syndrome, sarcopenia, and osteoporosis [15]. Furthermore, an important change associated with aging is a decline in immune system function and many aspects of aging involve inflammatory processes [16]. It is well known that a strong association between aging and chronic low-grade inflammatory activity might progress to long-term tissue damage and systemic chronic inflammation [17]. This latter could cause organ specific illness and, at the end, might increase the risk of mortality. With growing elderly populations and extended longevity in developed countries, there is increasing interest in elucidating the age-related inflammation processes. In addition, increasing incidence of obesity in industrialized countries can intensify this problem, due to known proinflammatory action induced by excess of abdominal adipose tissue [18]. On the opposite, calorie restriction diet, known to extend longevity, was recurrently shown to induce a low body weight, enhance the immune function, and ameliorate inflammation [19].
The most recent literature reports that GH is able to exert both anti- and proinflammatory activities in humans [20] and that inflammation can influence GH release and actions [21]. Studies in mice have demonstrated that blood levels of the proinflammatory cytokines, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) are reduced in long-lived GH-deficient and GH-resistant mice [22]. Moreover, circulating levels of adiponectin, an anti-inflammatory adipokine, are consistently elevated. This latter observation was unexpected, since the absence of GH signals in these mutants leads to increased adiposity, and because, in both animal models and humans, plasma levels of adiponectin were repeatedly shown to be inversely rather than directly related to adiposity [23]. According to this theory, hereditary GH resistance in an extensively evaluated population of individuals with Laron dwarfism in Ecuador has been associated with striking, nearly complete protection from cancer and diabetes [24]. Moreover, a cohort of GH-deficient dwarfs studied in Brazil was shown to be unexpectedly protected from atherosclerosis in spite of obesity and unfavorable serum lipid profiles [25]. In contrast, experiments in mice fed with high-fat diet (HFD)-induced obesity reported hypothalamic inflammation and gliosis [26]. The hypothalamus plays a fundamental role for the coordination of food intake and energy expenditure [27], with specialized neurons relaying information provided by leptin and insulin regarding fat depot sites to central mechanisms that regulate hunger and energy expenditure. Hypothalamic inflammation due to HFD-induced obesity has been associated with the development of secondary complications [28], and GH and IGF-1 axis have been described to play anti-inflammatory actions [29].
Since GH and IGF-1 can modulate inflammatory processes in both manners, no definitive conclusions can be drawn. Our data show the link between nonspecific inflammatory markers and IGF-1 levels, in a large adult population affected by obesity.
Obesity is associated with abnormalities of the GH/IGF-1 axis and the role of serum IGF-1 measurement for recognition of hypothalamic-pituitary disorders in obesity is still a matter of debate. Interestingly, skeletal maturation can be influenced by multiple factors and almost 25% of children affected by obesity show advanced bone age, associated with increased BMI Z-score, and one or more of the following altered values: insulin, leptin, DHEAS, IGF-1, and rate of weight gain [30]. No clear relationship or defined mechanisms of actions have been established, as yet, regarding the link that occurs among IGF-1, BMD, and obesity in adult population.
Our data demonstrate that higher levels of IGF-1 are associated with a lower inflammatory pattern and a higher BMD in adult obese individuals. IGF-1 seems to play a role in this homeostatic model of inflammation, aging, and bone health. Higher levels of IGF-1 were also associated with a better quality of life and lower degree of frailty in elderly subjects. IGF-1 may affect both muscle and bone through systemic and tissue specific signaling pathways. A trial by Terracciano et al. revealed that osteoporosis is related to muscle atrophy, which is linked with BMD and a reduced level of Akt, a component of the IGF-1/phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. In addition, abnormalities in GH/IGF-1 signaling have a negative effect on muscle and bone in elder subjects [31]. IGF-1 action is modulated by IGF-binding proteins (IGFBPs) which are secreted by muscle and might act on bone tissue.
In a cohort study, appendicular skeletal muscle mass correlated with cortical thickness and trabecular BMD. In that study, serum IGFBP-2 concentration was the most robust negative predictor of appendicular skeletal muscle [32]. The results of that trial led us to hypothesize that IGFBP-2 may bind to IGF-1 in the blood circulation and inhibit the beneficial effects of somatomedin on muscle and bone tissues. Moreover, in another trial, high IGFBP-2 circulating concentrations were associated with lower BMD in men and women [33].
Interestingly, IGF-1 has also been associated with inflammatory pattern in specific group of patients. For instance, an inverse relationship between inflammation and IGF-1 availability was observed in a clinical trial on HIV patients. In the study, inflammatory mediators showed positive correlations with IGFBP1/IGFBP2 and negative correlations with IGF-1/IGF-2, indicating that inflammation suppresses IGF-1/IGF-2 production [34]. IGF-1 has also showed an active immune regulatory capability versus monocytes in inflammatory bowel disease murine models. This hormone can induce IL-10 expression in monocytes, suppressing proinflammatory pattern in colitis [35].
Our data suggest that this aspect of signaling status could also be evident in obese adults, where a proinflammatory status might be triggered by adipose tissue mediators. Finally, we observed a positive correlation between IGF-1 and osteocalcin, an important non-collagenic protein of the bone matrix, produced by osteoblasts and considered a marker of bone formation. As we previously published, in the same population, lean body mass strongly correlates with osteocalcin and IGF-1 levels in a positive manner [14]. In addition, other authors demonstrated that in obese premenopausal women, affected by abdominal obesity, 6-month treatment with injections of GH increases the levels of IGF-1 and P1NP, the last one being an important marker of bone formation, as well as OSCA [36]. In their elegant study, these authors observed that GH treatment reduced the amount of abdominal fat and increased preadipocyte factor 1 (Pref 1), a preadipocyte secreted factor that inhibits adipogenesis, modulates mesenchymal stem cells commitment to chondrocytes and osteoblasts, and inhibits their differentiation into adipocytes [36].
A link between bone, fat, and muscle has been previously described by our group [2, 15] as well by others. Several potential mechanisms have been proposed to explain the complex relationship among these mesenchymal-derived tissues. In fact, adipose tissue secretes various inflammatory cytokines (such as IL-6, TNF-α), which are thought to have adverse metabolic and skeletal consequences. Moreover, other mediators, such as leptin, resistin, and adiponectin, are also involved in bone metabolism as we have recently described in vitro model system elsewhere [37, 38].
We realize that there are some study limitations linked to the lack of data regarding correlation between IGF-1 levels and other inflammatory markers, such as proinflammatory cytokines in our population of obese individuals, however, recent data show correlation between GH/IGF-1 status and inflammation in healthy volunteers [29].
In conclusion, our results show that higher levels of serum IGF-1 in adult obese patients are associated with lower inflammatory pattern and better skeletal homeostasis, as demonstrated by higher lumbar and femoral BMD and higher OSCA levels, leading to speculate the existence of a bone-adipose-muscle interplay in the modulation/regulation of energy/glucose homeostasis, skeletal metabolism, and chronic inflammation in adult subjects affected by abdominal obesity.
New research aimed to better clarify the link that occurs between body composition, GH/IGF-1 axis, inflammation status, and bone metabolism in obese subjects which are necessary, and they might lead to discover new lines of treatment of this pathological status.
References
World Health Organization Technical Report Series (2000) Obesity: preventing and managing the global epidemic. Report of a WHO consultation 894(i–xii):1–253
Migliaccio S, Greco EA, Aversa A et al (2014) Age-associated cardio metabolic diseases and cross-talk between adipose tissue and skeleton: endocrine aspects. Horm Mol Biol Clin Investig 20(1):25–38. doi:10.1515/hmbci-2014-0030
Cruz-Jentoft AJ, Baeyens JP, Bauer JM et al (2010) Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People. Age Ageing 39:412–423. doi:10.1093/ageing/afq034
Brown S, Rosen CJ (2003) Osteoporosis. Med Clin North Am 87:1039–1063
Zhao LJ, Jiang H, Papasian CJ et al (2008) Correlation of obesity and osteoporosis: effect of fat mass on the determination of osteoporosis. J Bone Miner Res 23(1):17–29. doi:10.1359/jbmr.070813
Cao JJ (2011) Effects of obesity on bone metabolism. J Orthop Surg Res 6:30. doi:10.1186/1749-799X-6-30
Møller N, Jørgensen JO (2009) Effects of growth hormone on glucose, lipid, and protein metabolism in human subjects. Endocr Rev 30:152–177. doi:10.1210/er.2008-0027
Junnila RK, List EO, Berryman DA et al (2013) The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol 9(6):366–376. doi:10.1038/nrendo.2013.67
Corpas E, Harman SM, Blackman MR (1993) Human growth hormone and human aging. Endocr Rev 14(1):20–39. doi:10.1210/edrv-14-1-20
Bartke A (2003) Can growth hormone (GH) accelerate aging? Evidence from GH transgenic mice. Neuroendocrinology 78(4):210–216
Finch CE, Crimmins EM (2004) Inflammatory exposure and historical changes in human life-spans. Science 305(5691):1736–1739. doi:10.1126/science.1092556
Bastard JP, Maachi M, Lagathu C et al (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17(1):4–12
Olefsky JM, Glass CK (2010) Macrophages, inflammation, and insulin resistance. Annu Rev Physiol 72:219–246
Fornari R, Francomano D, Greco EA et al (2015) Lean mass in obese adult subjects correlates with higher levels of vitamin D, insulin sensitivity and lower inflammation. J Endocrinol Invest 38(3):367–372. doi:10.1007/s40618-014-0189-z
Boyd CM, Ritchie CS, Tipton EF et al (2008) From bedside to bench: summary from the American Geriatrics Society/National Institute on Aging Research Conference on Comorbidity and Multiple Morbidity in Older Adults. Aging Clin Exp Res 20(3):181–188
Franceschi C, Bonafe M, Valensin S et al (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254
Bruunsgaard H, Pedersen M, Pedersen BK (2001) Aging and proinflammatory cytokines. Curr Opin Hematol 8(3):131–136
Park MH, Kim DH, Lee EK et al (2014) Age-related inflammation and insulin resistance: a review of their intricate interdependency. Arch Pharm Res 37(12):1507–1514. doi:10.1007/s12272-014-0474-6
Pahlavani MA (2004) Influence of caloric restriction on aging immune system. J Nutr Health Aging 8(1):38–47
Deepak DDC, Javadpour M, Clark D et al (2010) The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency. Growth Horm IGF Res 20:220–225. doi:10.1016/j.ghir.2010.02.002
Gaspari S, Marcovecchio ML, Breda L et al (2011) Growth in juvenile idiopathic arthritis: the role of inflammation. Clin Exp Rheumatol 29:104–110
Berryman DE, List EO, Coschigano KT et al (2004) Comparing adiposity profiles in three mouse models with altered GH signaling. Growth Horm IGF Res 14:309–318. doi:10.1016/j.ghir.2004.02.005
Wang Z, Al-Regaiey KA, Masternak MM et al (2006) Adipocytokines and lipid levels in Ames dwarf and caloric restricted mice. J Gerontol A Biol Sci Med Sci 61A:323–331
Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M et al (2011) Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med 3(70):70ra13. doi:10.1126/scitranslmed.3001845.
Oliveira JL, Aguiar-Oliveira MH, D’Oliveira A Jr et al (2007) Congenital growth hormone (GH) deficiency and atherosclerosis: effects of GH replacement in GH-naive adults. J Clin Endocrinol Metab 92:4664–4670. doi:10.1210/jc.2007-1636
Baquedano E, Ruiz-Lopez AM, Sustarsic EG et al (2014) The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice. Endocrinology 155(12):4856–4867. doi:10.1210/en.2014-1367
Flier JS (2004) Obesity wars: molecular progress confronts an expanding epidemic. Cell 116:337–350
Ferrante AW Jr (2007) Obesity-induced inflammation: a metabolic dialogue in the language of inflammation. J Intern Med 262:408–414. doi:10.1111/j.1365-2796.2007.01852.x
Andreassen M, Frystyk J, Faber J et al (2012) Growth hormone activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist. Eur J Endocrinol 166:811–819. doi:10.1530/EJE-11-1009
Klein KO, Newfield RS, Hassink SG (2015) Bone maturation along the spectrum from normal weight to obesity: a complex interplay of sex, growth factors and weight gain. J Pediatr Endocrinol Metab. doi:10.1515/jpem-2015-0234.
Terracciano C, Celi M, Lecce D et al (2013) Differential features of muscle fiber atrophy in osteoporosis and osteoarthritis. Osteoporos Int 24:1095–1100. doi:10.1007/s00198-012-1990-1
Lebrasseur NK, Achenbach SJ, Melton LJ 3rd et al (2012) Skeletal muscle mass is associated with bone geometry and microstructure and serum insulin-like growth factor binding protein-2 levels in adult women and men. J Bone Miner Res 27:2159–2169. doi:10.1002/jbmr0.1666
Amin S, Riggs BL, Melton LJ 3rd et al (2007) High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. J Bone Miner Res 22:799–807. doi:10.1359/jbmr.070306
Suh HS, Lo Y, Choi N et al (2015) Insulin-like growth factors and related proteins in plasma and cerebrospinal fluids of HIV-positive individuals. J Neuroinflamm 12:72. doi:10.1186/s12974-015-0288-6
Ge RT, Mo LH, Wu R et al (2015) Insulin-like growth factor-1 endues monocytes with immune suppressive ability to inhibit inflammation in the intestine. Sci Rep 5:7735. doi:10.1038/srep07735
Bredella MA, Gerweck AV, Barber LA et al (2014) Effects of growth hormone administration for 6 months on bone turnover and bone marrow fat in obese premenopausal women. Bone 62:29–35. doi:10.1016/j.bone.2014.01.022
Magni P, Dozio E, Galliera E, Ruscica M, Corsi M (2010) Molecular aspects of adipokine–bone interactions. Curr Mol Med 10:522–532
Bimonte VM, Fittipaldi S, Marocco C, Emerenziani GP, Fornari R, Guidetti L, Poggiogalle E, Nicolai E, Di Luigi L, Donini LM, Baldari C, Lenzi A, Greco EA, Migliaccio S (2016) Physical activity and hypocaloric diet recovers osteoblasts homeostasis in women affected by abdominal obesity. Endocrine. doi:10.1007/s12020-016-1193-1
Acknowledgements
Research was funded by PRIN 2009 2009KENS9K_004 to LMD, PRIN 2011 052013 to SM, PON 01_00829 to AL, and PRIN 072013. All authors have contributed significantly to the study and are in agreement with the content of the manuscript. All authors: concept/design, collection, and/or assembly of data. FD: data analysis. All authors: interpretation and critical revision of manuscript. All authors: final approval of manuscript.
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SM received speaker’s honorarium from Lilly, Bayer, Italfarmaco, MSD; AA received speaker’s honorarium from Lilly, Bayer. On behalf of all the authors, the corresponding author states that there is no conflict of interest.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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All subjects provided informed consent before taking part in the study, and the local ethical committee approved the research protocol.
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Rachele Fornari, Chiara Marocco and Davide Francomano are equally contributed to this work; Emanuela A. Greco and Silvia Migliaccio are equally contributed to this work.
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Fornari, R., Marocco, C., Francomano, D. et al. Insulin growth factor-1 correlates with higher bone mineral density and lower inflammation status in obese adult subjects. Eat Weight Disord 23, 375–381 (2018). https://doi.org/10.1007/s40519-017-0362-4
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DOI: https://doi.org/10.1007/s40519-017-0362-4