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Cardiac autonomic neuropathy as a result of mild hyper‐caloric challenge in absence of signs of diabetes: Modulation by anti‐diabetic drugs
Author(s) -
Bakkar Nour Mounira,
Mroueh Ali,
Ghali Rana,
AlAssi Ola,
Kaplan Abdullah,
Mougharbil Nahed,
Eid Ali,
Zouein Fouad,
ElYazbi Ahmed
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.697.7
Subject(s) - medicine , endocrinology , diabetes mellitus , pioglitazone , diabetic cardiomyopathy , metformin , metabolic syndrome , diabetic neuropathy , ampk , heart failure , type 2 diabetes , cardiomyopathy , biochemistry , chemistry , protein kinase a , enzyme
Cardiac autonomic neuropathy (CAN) is an early cardiovascular complication of diabetes occurring before signs of metabolic derangement are evident. The cause of CAN remains elusive and cannot be directly linked to hyperglycemia since pre‐diabetic and metabolic syndrome patients demonstrate signs of cardiac autonomic dysfunction. Recent clinical data report cardioprotective effects of some anti‐diabetic drugs independent of their hypoglycemic action. Significantly, pioglitazone and metformin demonstrated protection in pre‐diabetic patients. Here, we used a rat model receiving limited daily increase in calories from fat (HC diet) to assess whether mild metabolic challenge led to CAN in absence of interfering effects of hyperglycemia, glucose intolerance, or obesity. Compared to controls, rats receiving HC diet for 12 weeks showed reduction in baroreceptor sensitivity and heart rate variability despite lack of change in baseline hemodynamic and cardiovascular structural parameters. Impairment of cardiac autonomic control was accompanied with perivascular adipose inflammation observed as an increased interleukin‐1b (IL‐1b) and tumor necrosis factor‐a (TNF‐a) expression, together with increased cardiac oxidative stress, IL‐1b expression and signaling derangements characteristic of diabetic cardiomyopathy including reduction of AMPK phosphorylation and activation of the TGF‐b/Erk 1/2 pathway. At this stage, examination of the brainstem revealed no molecular disorders in support of an early, potentially reversible effect. Two‐week treatment with metformin or pioglitazone rectified the autonomic derangement and corrected the molecular changes in heart and adipose tissue. Switching rats on HC diet to normal chow but not to isocaloric amounts of HC for two weeks reversed CAN. As such, we conclude that adipose inflammation due to increased fat intake might underlie development of CAN and, hence, the beneficial effects of metformin and pioglitazone. Support or Funding Information Supported by AUB MPP fund #320148. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .