Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution

Doulamis, Ilias P.; Tzani, Aspasia; Konstantopoulos, Panagiotis; Daskalopoulou, A.; Spinos, Theodoros; Bletsa, Evanthia; Mitsopoulou, Dimitra; Spinou, Marianna; Brinia, Maria E; Palaiopanos, Konstantinos; Korou, Laskarina Maria; Perrea, Despina; Katsilambros, Nicholas

doi:10.1515/jbcpp-2018-0118

Cited by 8 publications

(7 citation statements)

References 12 publications

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“…In addition to alterations in triglyceride, cholesterol, LDL, and HDL levels, a decrease in FFA levels was also observed in our study. Consistently with previously reported data ( 45 , 46 ), the elevation of circulating insulin level and lower serum level of IGF-1 indicates that orchiectomy induced insulin resistance. Testosterone deficiency often accounts for negative effects on lipid and glucose metabolism, and some bone and skeletal metabolism comorbidities may be associated with these changes.…”

Section: Discussionsupporting

confidence: 92%

Quercetin Attenuates Osteoporosis in Orchiectomy Mice by Regulating Glucose and Lipid Metabolism via the GPRC6A/AMPK/mTOR Signaling Pathway

Sun

Pan

et al. 2022

Front. Endocrinol.

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Quercetin, a flavonoid found in natural medicines, has shown a role in disease prevention and health promotion. Moreover, because of its recently identified contribution in regulating bone homeostasis, quercetin may be considered a promising agent for improving bone health. This study aimed to elucidate the role of quercetin in androgen deprivation therapy-induced osteoporosis in mice. C57BL/6 mice were subjected to orchiectomy, followed by quercetin treatment (75 and 150 mg/kg/d) for 8 weeks. Bone microstructure was then assessed by micro-computed tomography, and a three-point bending test was used to evaluate the biomechanical parameters. Hematoxylin and eosin (H&E) staining was used to examine the shape of the distal femur, gastrocnemius muscle, and liver. The balance motion ability in mice was evaluated by gait analysis, and changes in the gastrocnemius muscle were observed via Oil red O and Masson’s staining. ELISA and biochemical analyses were used to assess markers of the bone, glucose, and lipid metabolism. Western blotting analyses of glucose and lipid metabolism-related protein expression was performed, and expression of the GPCR6A/AMPK/mTOR signaling pathway-related proteins was also assessed. After 8 weeks of quercetin intervention, quercetin-treated mice showed increased bone mass, bone strength, and improved bone microstructure. Additionally, gait analysis, including stride length and frequency, were significantly increased, whereas a reduction of the stride length and gait symmetry was observed. H&E staining of the gastrocnemius muscle showed that the cross-sectional area of the myofibers had increased significantly, suggesting that quercetin improves balance, motion ability, and muscle mass. Bone metabolism improvement was defined by a reduction of serum levels of insulin, triglycerides, total cholesterol, and low-density lipoprotein, whereas levels of insulin-like growth factor-1 and high-density lipoprotein were increased after quercetin treatment. Expression of proteins involved in glucose uptake was increased, whereas that of proteins involved in lipid production was decreased. Moreover, the GPRC6A and the phospho-AMPK/AMPK expression ratio was elevated in the liver and tibia tissues. In contrast, the phospho-mTOR/mTOR ratio was reduced in the quercetin group. Our findings indicate that quercetin can reduce the osteoporosis induced by testosterone deficiency, and its beneficial effects might be associated with the regulation of glucose metabolism and inhibition of lipid metabolism via the GPCR6A/AMPK/mTOR signaling pathway.

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Section: Discussionsupporting

confidence: 92%

Quercetin Attenuates Osteoporosis in Orchiectomy Mice by Regulating Glucose and Lipid Metabolism via the GPRC6A/AMPK/mTOR Signaling Pathway

Sun

Pan

et al. 2022

Front. Endocrinol.

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“…Our study was carried out in patients with hypogonadism. Low testosterone levels worsen peripheral insulinresistance and therefore push toward the development of T2DM [45]. More in detail, testosterone can influence carbohydrate, protein, and lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study

et al. 2020

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Background Overweight and obesity are increasingly spread in our society. Low testosterone levels are often present in these patients, the so-called metabolic hypogonadism, that further alters the metabolic balance in a sort of vicious cycle. Very low-calorie ketogenic diet (VLCKD) has been reported to efficiently reduce body weight, glycaemia, and the serum levels of insulin, glycated hemoglobin, but its effects on β-cell function and total testosterone (TT) levels are less clear. Aim To evaluate the effects of VLCKD on markers suggested to be predictive of β-cell dysfunction development, such as proinsulin or proinsulin/insulin ratio, and on TT values in a cohort of overweight or obese nondiabetic male patients with metabolic hypogonadism. Methods Patients with overweight or obesity and metabolic hypogonadism underwent to VLCKD for 12 weeks. Anthropometric parameters, blood testing for the measurement of glycaemia, insulin, C-peptide, proinsulin, TT, calculation of body-mass index (BMI), and HOMA index were performed before VLCKD and after 12 weeks. Results Twenty patients (mean age 49.3 ± 5.2 years) were enrolled. At enrollement all patients presented increased insulin, HOMA index, C-peptide, and proinsulin levels, whereas the proinsulin/insulin ratio was within the normal values. After VLCKD treatment, body weight and BMI significantly decreased, and 14.9 ± 3.9% loss of the initial body weight was achieved. Glycaemia, insulin, HOMA index, C-peptide, and proinsulin significantly decreased compared to pre-VLCKD levels. Serum glycaemia, insulin, C-peptide, and proinsulin levels returned within the normal range in all patients. No difference in the proinsulin/insulin ratio was observed after VLCKD treatment. A mean increase of 218.1 ± 53.9% in serum TT levels was achieved and none of the patients showed TT values falling in the hypogonadal range at the end of the VLCKD treatment. Conclusions This is the first study that evaluated the effects of VLCKD on proinsulin, proinsulin/insulin ratio, and TT levels. VLCKD could be safely used to improve β-cell secretory function and insulin-sensitivity, and to rescue overweight and obese patients from β-cell failure and metabolic hypogonadism.

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“…Hormonal balance is an important factor for maintaining homeostasis, and endocrine alterations can lead to disease development. Indeed, OVX and ORX have been used as rodent models for inducing sarcopenia, due to reduced levels of estrogen and testosterone, respectively [ 16 , 39 , 40 , 41 , 42 ]. In our study, according to that described previously in the literature, OVX led to an increase in body weight gain [ 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

“…Surgical castration was used as rodent models for inducing sarcopenia and sarcopenia-related functional changes, due to reduced levels of estrogen and testosterone, as it occurs in menopause and andropause [ 16 , 39 , 40 , 41 , 42 ].…”

Section: Methodsmentioning

confidence: 99%

Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice

et al. 2021

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Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice.

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Experimental hypogonadism: insulin resistance, biochemical changes and effect of testosterone substitution

Cited by 8 publications

References 12 publications

Quercetin Attenuates Osteoporosis in Orchiectomy Mice by Regulating Glucose and Lipid Metabolism via the GPRC6A/AMPK/mTOR Signaling Pathway

Quercetin Attenuates Osteoporosis in Orchiectomy Mice by Regulating Glucose and Lipid Metabolism via the GPRC6A/AMPK/mTOR Signaling Pathway

The ketogenic diet corrects metabolic hypogonadism and preserves pancreatic ß-cell function in overweight/obese men: a single-arm uncontrolled study

Combined Effects of Exercise and Phytoanabolic Extracts in Castrated Male and Female Mice

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