Jelenik 2014 Diabetologie und Stoffwechsel
|Jelenik T, Bottermann K, Moellendorf S, Goedecke A, Kotzka J, Kelm M, Roden M, Szendroedi J (2014) Mice with insulin resistance and non-alcoholic fatty liver are characterized by cardiac hypertrophy and increased oxidative stress. Diabetologie und Stoffwechsel 9:250.|
Abstract: Non-alcoholic fatty liver (NAFL) and insulin resistance increase the risk of cardiac mortality and associate with impaired muscular and hepatic mitochondrial function. We hypothesized that also cardiac energy metabolism is altered in mice with insulin resistance and NAFL.
Mice with adipose tissue-specific overexpression of the sterol regulatory-element binding protein-1c, which have lipodystrophy and develop NAFL (NAFL), and wild-type controls (CON), underwent hyperinsulinemic-euglycemic clamps to assess insulin sensitivity (IS, n = 5 – 7). Systolic blood pressure was measured with catheters introduced into the left ventricle. Mitochondrial respiration and H2O2 production from cardiac mitochondria were assessed by high-resolution respirometry and the Amplex Red method, respectively (n = 7).
Peripheral and hepatic IS were lower in NAFL mice compared to CON (-71% and -70%; p < 0.05). Accordingly, NAFL mice were hyperglycemic (216 ± 36 vs. 108 ± 14 mg/dl, p < 0.05), hyperinsulinemic (76 ± 17 vs. 12 ± 5µU/ml, p < 0.05) and dyslipidemic (fatty acids: 1.17 ± 0.2 vs. 0.73 ± 0.44 mmol/l, p < 0.05). Heart to body weight ratio was increased by 34%, while blood pressure was unchanged. Glycolysis- and β-oxidation-derived mitochondrial oxidative capacity was increased by 93% (2.86 ± 0.06, CON: 1.47 ± 0.43 nmol/mg protein/s; p < 0.05) and by 125% (2.45 ± 0.66, CON: 1.09 ± 0.22 nmol/mg protein/s; p < 0.05) in the heart of NAFL mice, respectively. H2O2 production by mitochondrial complex III was 51% higher (p < 0.05), compared to age-matched CON.
Insulin resistance in mice with hepatic steatosis associates with non-hypertensive cardiac hypertrophy and increased energy demand of heart. Accumulation of oxidative stress, as a result of increased mitochondrial respiration, could render hearts vulnerable for ischemic intolerance and impaired myocardial function.
• Keywords: Amplex Red
• O2k-Network Lab: DE Duesseldorf Roden M
Labels: MiParea: Respiration Pathology: Diabetes