Toll-like receptor 4 (TLR4) as a possible pathological mechanism in hyperglycemia-associated testicular dysfunction

Naas, Huda; Oliveira, Amanda Almeida de; Karpova, Tatiana; Nunes, Kênia Pedrosa

doi:10.1016/j.mehy.2019.04.010

Cited by 16 publications

(7 citation statements)

References 65 publications

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“…In our study, a strong correlation between blood glucose reduction and TT increase was evident, suggesting that the restriction of carbohydrates (and food quantity) followed by robust blood glucose reduction may abrogate the expected TT decrease induced by feeding. Moreover, several studies have demonstrated that hyperglycaemia may hamper steroidogenesis and testis function by triggering oxidative stress and inflammation, 42,43 and in this study, higher glucose levels during OGTT were observed in hypogonadal subjects as compared with eugonadal subjects. Thus, it is possible that the efficacy of VLCKD in improving the HPG axis (i.e.…”

Section: Discussionsupporting

confidence: 62%

Very low‐calorie ketogenic diet rapidly augments testosterone levels in non‐diabetic obese subjects

et al. 2022

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Background:The very low-calorie ketogenic diet (VLCKD) represents an opportunity to attain clinically relevant weight loss in obese patients. Functional hypogonadism represents a frequent hormonal disorder associated with obesity and visceral fat accumulation characterised by low testosterone levels and subnormal luteinising hormone (LH) levels.Aim: To evaluate the early effects of VLCKD on serum total testosterone (TT) levels in non-diabetic obese patients.Methods: Twenty-two obese male patients (mean age 39.3 ± 11.7 years, mean body mass index (BMI) 38.2 ± 6.4 kg/m 2 ) were enrolled and treated for 28 days with VLCKD.Anthropometric and hormonal variables were assessed before, during and after diet intervention.Results: After 7 and 28 days on a VLCKD, a significant and persistent reduction in body weight, BMI, fat mass, blood glucose, insulin and homeostasis model assessment index was observed compared with baseline. TT significantly increased after 7 days (+35 ± 64 ng/dl) and 28 days (+74 ± 97 ng/dl) on a VLCKD. In addition to TT, a significant increase in serum sex hormone-binding globulin levels was observed after 7 (+2.1 ± 4.1) and 28 days (+7.7 ± 10.0). However, both calculated free testosterone and LH did not change after 7 or 28 days of VLCKD. Following cessation of VLCKD, hypogonadal subjects achieved a higher percentage of total weight loss (8.5% ± 1.5%), a greater reduction in weight (−9.94 ± 1.66 kg), fat mass (−7 ± 2.1 kg) and waist circumference (−6.31 ± 2.65 cm) and a greater improvement in glycaemia (−8.75 ± 10.92 mg/dl) as compared with eugonadal subjects. Furthermore, hypogonadal subjects exhibited a trend of higher TT increase (+98.12 ± 71.51 ng/dl) as compared with eugonadal subjects.Conclusions: VLCKD results in rapid improvements in TT levels associated with weight loss in male obese non-diabetic subjects, particularly in the presence of obesity-related hypogonadism.

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Section: Discussionsupporting

confidence: 62%

Very low‐calorie ketogenic diet rapidly augments testosterone levels in non‐diabetic obese subjects

et al. 2022

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“…The expression of TLRs has been investigated in epithelial cells of different tissues, such as those of the reproductive tracts. Specifically, TLRs expression was identified in adult human testis [10,11], showing that TLR2, 3 [12], and 4 [13] are highly expressed. Mouse Sertoli cells highly express TLR2, 3, 4, and 5 [14], which can be activated by their agonists and may initiate innate immune responses, inducing increased chemokine monocyte chemotactic protein (MCP)-1 and InterCellular Adhesion Molecule (ICAM)-1 expression [15,16].…”

Section: Introductionmentioning

confidence: 99%

The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

et al. 2021

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Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.

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“…This disease also regards as one of the important cause of morbidity and mortality worldwide Moreover, growing evidence suggests that DM is closely associated with fertility problems, particularly in the male [29]. In fact, previous clinical and pre-clinical studies have reported that DM causes serious disruptions in male reproductive function by paving the way for problems such as testicular tissue defects [29,30]. Similar to the literature, the results of our histopathological examination (JTBS) revealed that DM was dramatically disrupted histo-architecture of the testicular tissue and caused histopathological alterations such as seminiferous tubular atrophy, tubular degeneration, interstitial edema and Leydig cells losses.…”

Section: Discussionmentioning

confidence: 99%

Is losartan a promising agent for the treatment of type 1 diabetes-induced testicular germ cell apoptosis in rats?

et al. 2022

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Background: Diabetes mellitus (DM) is common metabolic disease that poses a major risk to public health and fertility. Previous studies indicate that DM may cause male infertility by triggering oxidative stress and germ cell apoptosis in the testis. Present study aimed to investigate the possible antiapoptotic effect of losartan against DM-induced testicular germ cell apoptosis.Methods and Results:Expreimental DM model was induced by intraperitoneal injection of streptozocin (STZ, 55 mg/kg) to 28 rats, which were then randomly assigned to 4 groups; 1 mL saline solution was given to DM+saline group by oral gavage, 5 mg/kg/day oral losartan was given to DM+low-dose losartan, 20 mg/kg/day oral losartan was given to DM+mid-dose losartan and, 80 mg/kg/day oral losartan was given to DM+high-dose losartan group for 4 weeks. Bax, Bcl-2 and cleaved-Caspase 3 immunoexpression, terminal-deoxynucleotidyl transferase dutp nick end labeling (TUNEL), Annexin-V and Real Time PCR analyses performed to evaluate antiapoptotic effects of losartan on diabetic rats' testis. In addition, biochemical analyzes carried out to evaluate change in oxidative stress. Conclusion:The results showed that losartan may have dose-related antiapoptotic effects on rats' testis via decreasing oxidative stress.

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Toll-like receptor 4 (TLR4) as a possible pathological mechanism in hyperglycemia-associated testicular dysfunction

Cited by 16 publications

References 65 publications

Very low‐calorie ketogenic diet rapidly augments testosterone levels in non‐diabetic obese subjects

Very low‐calorie ketogenic diet rapidly augments testosterone levels in non‐diabetic obese subjects

The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Is losartan a promising agent for the treatment of type 1 diabetes-induced testicular germ cell apoptosis in rats?

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