Poster Topical Area: Diet and Cancer
Poster Board Number: 181
Objective: To demonstrate that glucose homeostasis alterations due to paternal high fat diet (HFD), may be transmitted to the offspring, being associated to overexpression of the hepatic type 1 cannabinoid/endocannabinoid receptor (CB1R). This objective is supported by previous knowledge indicating that CB1R present in hepatocytes is required for development of insulin resistance (IR), and that HFD leads to chronic overactivity of the endocannabinoid system in different tissues.
Methods and animal treatment: Ten weeks old male mice (C57BL/6) were fed a HFD (fat: 60% Kcal) during 6 weeks (mF0). Then, males were mated with mature females (fF0) eating an isocaloric control diet (fat: 10% Kcal). The offspring was fF1 and mF1 according to sex. At 45 days old, fF1 and mF1 mice were fed a control or HFD during 8 weeks (thus we had C-mF1; C-fF1 and HFD-mF1; HFD-fF1). Five fF1 and mF1 were subjected to an insulin sensitivity (IST) test and a pyruvate tolerance test (PTT) to obtain glycemia curves (0-120min) after insulin or Na-pyruvate intraperitoneal injection. Mice were sacrificed, livers extracted, and immediately frozen in liquid nitrogen. Subsequently, livers were ground frozen and homogenized for determination of CB1R mRNA by real time RT-PCR and protein abundance by Western blot analysis (WB).
Results: HFD-mF1 showed a clear IR state in comparison to C-mF1, which is not observed in HFD-fF1 where not significantly values of glycemia were observed in comparison to C-fF1 during the test period. The PPT, to test gluconeogenesis (GNG), gave similar high values of glycemia in C-mF1 and HFD-mF1; conversely, HFD-fF1 glycemia levels were significantly higher than those in C-mF1. Moreover, PPT showed higher glycemia in HFD-mF1 than C-fF1 and HFD-fF1, and C-mF1 higher than C-fF1. Hepatic CB1R mRNA levels were similar in HFD-mF1 and C-mF1, and were decreased by 80% compared to a normal male. In C-fF1, level of CB1R mRNA was as a normal female and significantly higher by 100% than level in HFD-fF1. Present experiments involves WB.
Conclusion: Glucose homeostasis alterations (IR and exacerbated GNG) are transmitted mainly to male offspring from fathers fed a HFD. Surprisingly, this fact is not related to levels of CB1R mRNA present in liver of mF1. Whether it is related to hepatic CB1R protein abundance is currently under investigation.
Academic position. Professor, Senior Scientist
Universidad de Chile
Santiago, Region Metropolitana, Chile