PMID- 34656705
OWN - NLM
STAT- MEDLINE
DCOM- 20220314
LR  - 20220314
IS  - 1873-1708 (Electronic)
IS  - 0890-6238 (Linking)
VI  - 106
DP  - 2021 Dec
TI  - Repression of HDAC5 by acetate restores hypothalamic-pituitary-ovarian function 
      in type 2 diabetes mellitus.
PG  - 69-81
LID - S0890-6238(21)00164-7 [pii]
LID - 10.1016/j.reprotox.2021.10.008 [doi]
AB  - Type 2 diabetes mellitus (T2DM) accounts for 90-95 % of worldwide diabetes cases 
      and is primarily characterized by insulin resistance. Its progression as a 
      chronic metabolic disease has been largely associated with female reproductive 
      abnormalities, including ovarian dysfunction with consequent infertility. 
      Epigenetic modifications have been suggested as a possible link to metabolic 
      comorbidities. We therefore hypothesized that short chain fatty acids, acetate 
      (ACA), a potential histone deacetylase inhibitor (HDAC) ameliorates 
      hypothalamic-pituitary-ovarian (HPO) dysfunction in T2DM. Female Wistar rats 
      weighing 160-190 g were allotted into three groups (n = 6/group): Control 
      (vehicle; po), T2D and T2D + ACA (200 mg/kg; po). T2DM was induced by fructose 
      administration (10 %; w/v) for 6 weeks and single dose of streptozotocin (35 
      mg/kg; ip). The present data showed that in addition to insulin resistance, 
      increased fasting blood glucose and insulin, T2DM induced elevated plasma, 
      hypothalamic and ovarian triglyceride, lipid peroxidation, TNF-alpha and glutathione 
      depletion. Aside, T2DM also led to increased plasma lactate production and 
      gamma-Glutamyl transferase as well as decreased gonadotropins/17beta-estradiol. 
      Histologically, hypothalamus, pituitary and ovaries revealed disrupted neuronal 
      cells/moderate hemorrhage, altered morphology/vascular congestions, and 
      degenerated antral follicle/graafian follicle with mild fibrosis and infiltrated 
      inflammatory cells respectively in T2D animals. Interestingly, these alterations 
      were accompanied by elevated plasma/hypothalamic HDAC5 and attenuated when 
      treated with acetate. The present results demonstrate that T2DM induces HPO 
      dysfunction, which is accompanied by elevated circulating/hypothalamic HDAC5. The 
      results in addition suggest that acetate restores HPO function in T2DM by 
      suppression of HDAC5 and enhancement of insulin sensitivity.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Olaniyi, Kehinde S
AU  - Olaniyi KS
AD  - Cardio/Repro-metabolic and Microbiome Research Unit, Department of Physiology, 
      College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 
      360101, Nigeria; School of Laboratory Medicine & Medical Sciences, Nelson R 
      Mandela School of Medicine, University of KwaZulu-Natal, Private Bag X54001, 
      Congella 4013, Westville, Durban, South Africa. Electronic address: 
      olaniyisk@abuad.edu.ng.
FAU - Amusa, Oluwatobi A
AU  - Amusa OA
AD  - Cardio/Repro-metabolic and Microbiome Research Unit, Department of Physiology, 
      College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, 
      360101, Nigeria.
FAU - Ajadi, Isaac O
AU  - Ajadi IO
AD  - School of Laboratory Medicine & Medical Sciences, Nelson R Mandela School of 
      Medicine, University of KwaZulu-Natal, Private Bag X54001, Congella 4013, 
      Westville, Durban, South Africa.
FAU - Alabi, Bolanle Y
AU  - Alabi BY
AD  - Department of Hematology and Virology, University of Medical Sciences Teaching 
      Hospital Complex, Akure, Nigeria.
FAU - Agunbiade, Toluwani B
AU  - Agunbiade TB
AD  - Department of Medical Microbiology and Parasitology, College of Medicine and 
      Health Sciences, Afe Babalola University, Ado-Ekiti, 36010, Nigeria.
FAU - Ajadi, Mary B
AU  - Ajadi MB
AD  - Department of Chemical Pathology, College of Health Sciences, Ladoke Akintola 
      University of Technology, Ogbomoso, Nigeria; Department of Medical Biochemistry, 
      School of Laboratory Medicine, University of KwaZulu-Natal, Private Bag X54001, 
      Congella 4013, Westville, Durban, South Africa.
LA  - eng
PT  - Journal Article
DEP - 20211014
PL  - United States
TA  - Reprod Toxicol
JT  - Reproductive toxicology (Elmsford, N.Y.)
JID - 8803591
RN  - 0 (Acetates)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Triglycerides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.5.1.98 (Hdac5 protein, rat)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Acetates/*pharmacology
MH  - Animals
MH  - Diabetes Mellitus, Experimental/physiopathology
MH  - Diabetes Mellitus, Type 2/*physiopathology
MH  - Female
MH  - Histone Deacetylase Inhibitors/*pharmacology
MH  - Histone Deacetylases/*physiology
MH  - Hypothalamo-Hypophyseal System/*drug effects/physiopathology
MH  - Lipid Peroxidation
MH  - Ovary/*drug effects/physiopathology
MH  - Rats
MH  - Rats, Wistar
MH  - Triglycerides/metabolism
MH  - Tumor Necrosis Factor-alpha/analysis
OTO - NOTNLM
OT  - HDAC
OT  - Hypothalamic-pituitary-gonadal axis
OT  - Metabolic disease
OT  - Short chain fatty acids
OT  - Type 2 diabetes mellitus
EDAT- 2021/10/18 06:00
MHDA- 2022/03/15 06:00
CRDT- 2021/10/17 20:39
PHST- 2021/07/10 00:00 [received]
PHST- 2021/10/01 00:00 [revised]
PHST- 2021/10/11 00:00 [accepted]
PHST- 2021/10/18 06:00 [pubmed]
PHST- 2022/03/15 06:00 [medline]
PHST- 2021/10/17 20:39 [entrez]
AID - S0890-6238(21)00164-7 [pii]
AID - 10.1016/j.reprotox.2021.10.008 [doi]
PST - ppublish
SO  - Reprod Toxicol. 2021 Dec;106:69-81. doi: 10.1016/j.reprotox.2021.10.008. Epub 
      2021 Oct 14.