Rescue effect of sodium acetate in diabetes mellitus-associated testicular dysfunction is accompanied by PCSK9 modulation

Kehinde S Olaniyi; Olabimpe C Badejogbin; Salam B Saliu; Lawrence A Olatunji

doi:10.1016/j.biochi.2021.02.004

Rescue effect of sodium acetate in diabetes mellitus-associated testicular dysfunction is accompanied by PCSK9 modulation

Biochimie. 2021 May:184:52-62. doi: 10.1016/j.biochi.2021.02.004. Epub 2021 Feb 10.

Authors

Kehinde S Olaniyi¹, Olabimpe C Badejogbin², Salam B Saliu³, Lawrence A Olatunji³

Affiliations

¹ Cardio/Repro-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 360101, Nigeria; HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, 240001, Nigeria. Electronic address: olaniyisk@abuad.edu.ng.
² Cardio/Repro-metabolic and Microbiome Research Unit, Department of Physiology, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 360101, Nigeria; Department of Physiology, College of Medicine, University of Lagos, 100213, Lagos, Nigeria.
³ HOPE Cardiometabolic Research Team & Department of Physiology, College of Health Sciences, University of Ilorin, Ilorin, 240001, Nigeria.

PMID: 33581194
DOI: 10.1016/j.biochi.2021.02.004

Abstract

Diabetes mellitus (DM) is a global health burden, affecting about 463 million of the adult population worldwide. Approximately 94% of diabetic male individuals develop varying degrees of testicular disorders (TDs), which usually result in hypogonadism, hypotestosteronemia and defective spermatogenesis and steroidogenesis. Short chain fatty acids (SCFAs) have shown potential benefits in metabolic health. However, its effect on TD associated with DM is not clear. Howbeit, the present study investigated the hypothesis that SCFAs, acetate would ameliorate TD accompanying DM, possibly by suppressing proprotein convertase subtilisin/kexin type 9 (PCSK9). Male Wistar rats (210-240 g) were allotted into groups (n = 6/group): control (vehicle; po), DM with/without 200 mg/kg (po) of sodium acetate (SAc). Diabetes was induced by streptozotocin 65 mg/kg (iv) after a dose of nicotinamide (110 mg/kg). Semen/biochemical and histological analyses were performed with appropriate methods. In addition to hyperglycemia, hyperinsulinemia and reduced insulin sensitivity, DM led to increased serum and testicular triglyceride or total cholesterol/high-density lipoprotein cholesterol ratio, low-density lipoprotein cholesterol, malondialdehyde, TNF-α, IL-6 and PCSK9 as well as reduced high-density lipoprotein cholesterol and glutathione. Moreover, DM caused TD which is characterized by altered sperm parameters, disrupted tissue architecture, atrophied seminiferous tubules, deleterious spermatogonia, disappearance of lumen and cellular degeneration as well as decreased luteinizing hormone and testosterone. However, the administration of SAc attenuated these alterations. The study demonstrates that DM-induced TD is accompanied by elevated PCSK9. The results however suggest that SAc rescues testicular disorder/dysfunction associated with DM by suppression of PCSK9 and improvement of insulin sensitivity.

Keywords: Diabetes mellitus; Metabolism; PCSK9; Sperm; Testicular dysfunction; Testosterone.

MeSH terms

Animals
Diabetes Mellitus, Experimental / enzymology*
Diabetes Mellitus, Experimental / pathology
Male
Proprotein Convertase 9 / metabolism*
Rats
Rats, Wistar
Sodium Acetate / pharmacology*
Testicular Diseases / enzymology*
Testicular Diseases / pathology
Testis / enzymology*
Testis / pathology

Substances

Sodium Acetate
PCSK9 protein, rat
Proprotein Convertase 9