Androgens and Adipose Tissue in Males: A Complex and Reciprocal Interplay

Mammi, Caterina; Calanchini, Matilde; Antelmi, Antonella; Cinti, Francesca; Rosano, Giuseppe; Lenzi, Andrea; Caprio, Massimiliano; Fabbri, Andrea

doi:10.1155/2012/789653

Cited by 78 publications

(85 citation statements)

References 89 publications

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“…However, the HFS rats also showed a decrease in plasma testosterone levels, a finding consistent with previous clinical reports which demonstrated that obesity in men is associated with low testosterone levels (Barrett-Connor 1992, Andersson et al 1994, Grossmann 2013, Mogri et al 2013. The reduction of testosterone levels in the HFS rats could be a factor in the decrease in the hypothalamo-pituitary-gonadal axis due to inflammation following obesity as decribed in previous studies (Cohen 1999, Gregor & Hotamisligil 2011, Mammi et al 2012, Jayaraman et al 2014b. Although it has been shown that obesity could increase the estrogen levels in female rats (Pratchayasakul et al 2011), our previous study demonstrated that 12 weeks of high-fat diet feeding did not affect the circulating estrogen levels in male rats (Pratchayasakul et al 2011).…”

Section: Discussionsupporting

confidence: 88%

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats

Potikanond¹,

Rattanachote²,

Pintana³

et al. 2016

Journal of Endocrinology

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The present study aimed to test the hypothesis that testosterone deprivation impairs osteoblastic insulin signaling, decreases osteoblast survival, reduces bone density, and that obesity aggravates those deleterious effects in testosterone-deprived rats. Twenty four male Wistar rats underwent either a bilateral orchiectomy (O, nZ12) or a sham operation (S, nZ12). Then the rats in each group were further divided into two subgroups fed with either a normal diet (ND) or a high-fat diet (HF) for 12 weeks. At the end of the protocol, blood samples were collected to determine metabolic parameters and osteocalcin ratios. The tibiae were collected to determine bone mass using microcomputed tomography and for osteoblast isolation. The results showed that rats fed with HF (sham-operated HF-fed rats (HFS) and ORX HF-fed rats (HFO)) developed peripheral insulin resistance and had decreased trabecular bone density. In ND-fed rats, only the ORX ND-fed rats (NDO) group had decreased trabecular bone density. In addition, osteoblastic insulin resistance, as indicated by a decrease in tyrosine phosphorylation of the insulin receptor and Akt, were observed in all groups except the sham-operated ND-fed rats (NDS) rats. Those groups, again with the exception of the NDS rats, also had decreased osteoblastic survival. No differences in the levels of osteoblastic insulin resistance and osteoblastic survival were found among the NDO, HFS, and HFO groups. These findings suggest that either testosterone deprivation or obesity alone can impair osteoblastic insulin signaling and decrease osteoblastic survival leading to the development of osteoporosis. However, obesity does not aggravate those deleterious effects in the bone of testosterone-deprived rats.

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Section: Discussionsupporting

confidence: 88%

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats

Potikanond¹,

Rattanachote²,

Pintana³

et al. 2016

Journal of Endocrinology

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“…[6] However, it is unclear whether plasma leptin level affects the production of testosterone or dihydrotestosterone in the local environment of hair follicles, which has more implication in the development of AGA than systemic androgens. [7] The interaction between dermal adipose tissue and hair follicles is receiving more attention currently.…”

Section: It Is Known That Excess Of Plasma Leptin Has a Negative Impamentioning

confidence: 99%

Higher plasma leptin is associated with higher risk of androgenetic alopecia in men

Yang

Chung

Lin

et al. 2017

Experimental Dermatology

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In addition to genetics and androgens, novel factors could play a role in androgenetic alopecia (AGA). This study aims to investigate the association between plasma leptin level with the risk and severity of AGA in men. Forty-eight subjects were enrolled including 29 AGA and 19 non-AGA subjects. The plasma leptin level was significantly higher in AGA subjects, compared to non-AGA subjects (4.45 vs 2.76 ng/mL, P<.05).A higher plasma leptin levels were positively correlated with the risk of developing AGA in multivariate logistic analysis (odds ratio=2.77, P<.05). Leptin from the circulation might impact the development of AGA. | BACKGROUNDAndrogenetic alopecia (AGA) is regarded as an androgen-mediated process that occurs in genetically susceptible patients. However, factors other than androgens are believed to be involved in the pathogenesis of AGA because anti-androgen treatment does not completely reverse miniaturization. [1] Our previous study in men with AGA revealed that obesity is associated with a higher severity of hair loss.[2] Those findings suggested that obesity-associated metabolic changes could be a modulator for the progression of AGA. Leptin is a major adipocyte-derived factor, and its plasma level is commonly up-regulated in obese subjects due to the increased adipose tissue and the concomitant development of central leptin resistance. [3] Leptin has been reported to modulate the growth of hair follicles. [4,5] | QUESTIONS ADDRESSEDWe hypothesize that systemic leptin levels might modulate the growth of hair follicles and subsequently impact the development and severity of hair diseases. Therefore, we conducted the current study to investigate the association between plasma leptin levels with the risk and severity of AGA in men. | EXPERIMENTAL DESIGNMale subjects who were diagnosed as male pattern AGA or healthy volunteers with no history of AGA (non-AGA) at the age of 20-50 years were included in this study. The details of exclusion criteria and assessment of AGA are summarized in Data S1. The blood samples were taken from all subjects in the early morning after 8 hours of fasting.Enzyme-linked immunoassay kits were then used for the quantification of plasma levels of leptin, adiponectin, testosterone, insulin-like growth factor-1 (IGF-1) and transforming growth factor-β1 (TGF-β1). | RESULTSA total of 48 subjects were enrolled in this study including 29 subjects with AGA and 19 non-AGA control subjects. The mean age of AGA subjects was 28.8 years and non-AGA subjects 34.1 years. Among the AGA subjects, 17 of them were diagnosed as mild severity (grade 2-3) and 12 subjects advanced severity (grade 4-6).BMI was not significantly different between AGA and non-AGA subjects ( Figure 1A) and was not correlated with the onset of AGA Abbreviations: AGA, androgenetic alopecia; BMI, body mass index; IGF, insulin growth factor;OR, odds ratio; TGF, transforming growth factor.F I G U R E 1 BMI and plasma leptin level in AGA group (AGA+) vs non-AGA group (AGA-) and mild AGA group vs severe AGA group...

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Section: Dear Sirmentioning

confidence: 99%

“…1 The main endocrine derangements of KS include decreased secretion of androgens, increased plasma gonadotrophins, small testes and azoospermia. 1 Patients with KS have a higher prevalence of metabolic syndrome (MetS) and cardiovascular abnormalities, accounting for the increased risk of dying from heart disease. [1][2][3] MetS is closely associated with a low-grade chronic inflammatory status characterized by abnormal cytokine production, which activates a network of inflammatory signalling pathways.…”

Section: Dear Sirmentioning

confidence: 99%

“…1 Patients with KS have a higher prevalence of metabolic syndrome (MetS) and cardiovascular abnormalities, accounting for the increased risk of dying from heart disease. [1][2][3] MetS is closely associated with a low-grade chronic inflammatory status characterized by abnormal cytokine production, which activates a network of inflammatory signalling pathways. CCL2 is a major chemokine produced by monocytes, dendritic cells and macrophages and is crucial for the induction of chronic low-grade inflammation by accelerating macrophage infiltration in adipose tissue.…”

Section: Dear Sirmentioning

confidence: 99%

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The Authors' Reply: Oestradiol concentrations are not elevated in obesity‐associated hypogonadotrophic hypogonadism

Aftab

Kumar

Barber

2013

Clinical Endocrinology

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The Authors' Reply: Oestradiol concentrations are not elevated in obesity-associated hypogonadotrophic hypogonadismWe would like to thank Dhindsa and colleagues for their interest and comments on our recent review article published in Clinical Endocrinology entitled 'The Role of Obesity and Type 2 Diabetes Mellitus in the development of Male Obesity-associated Secondary Hypogonadism'. We would also like to thank the Editor for the opportunity to respond. We would like to confirm that we agree with the useful comments raised and provide further comment below.In our published review, we commented that the mechanisms implicated in the pathogenesis of secondary hypogonadism in men and its association with obesity and type 2 diabetes mellitus are multiple, complex and incompletely understood. We also stated that one of the pathogenic mechanisms implicated in the development of male obesity-associated secondary hypogonadism is increased aromatase activity within adipocytes. This results in increased peripheral conversion of testosterone into oestradiol and subsequent negative feedback on secretion of luteinizing hormone secretion from the pituitary. The suppressive effect of such a mechanism on the male hypothalamo-pituitary-gonadal axis results in a reduction in plasma testosterone levels and secondary hypogonadism. Consistent with this hypothesis, it has been reported in the literature that obese men show increased levels of oestrogens and decreased levels of bioavailable androgens within the serum. 1 It has also been noted that use of aromatase inhibitors in men with obesity-related hypogonadism may normalize serum testosterone, again consistent with an important pathogenic role for aromatization in this condition. 2 However, we acknowledge that there is controversy in the literature regarding the role of aromatization in the pathogenesis of male obesity-associated secondary hypogonadism. There is some inconsistency in the literature regarding relationships between serum levels of testosterone and oestradiol and the severity of obesity in this condition. We acknowledge that in some studies on obese men, serum levels of free oestradiol directly correlate with free testosterone. 3,4 One explanation for this direct correlation is that with increasing obesity in men, as serum levels of testosterone fall (following suppression of the male gonadal axis), serum oestradiol levels would also be expected to fall eventually due to lack of substrate (testosterone) for the aromatase enzyme. This hypothesis has been supported by the European Male Ageing Study. 3,4 We feel that it is important to emphasize that there are many potential mechanisms that underlie the complex pathogenesis of male obesity-associated secondary hypogonadism other than enhanced aromatase activity, as outlined in our published review article. These include the increasingly important roles of leptin, inflammatory mediators (TNF-a, IL-1b, CRP), the role of sleep disruption and the serotoninergic system and endogenous kisspeptin. We also outline the effects o...

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Androgens and Adipose Tissue in Males: A Complex and Reciprocal Interplay

Cited by 78 publications

References 89 publications

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats

Obesity does not aggravate osteoporosis or osteoblastic insulin resistance in orchiectomized rats

Higher plasma leptin is associated with higher risk of androgenetic alopecia in men

The Authors' Reply: Oestradiol concentrations are not elevated in obesity‐associated hypogonadotrophic hypogonadism

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