Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring

Maternally inherited familial hypercholesterolemia（FH） impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH.However,it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance.In this study,we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice.Apo CIII transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring：maternal non-transgenic control and maternal transgenic offspring,and paternal control and paternal transgenic offspring.Plasma triglycerides（TG）,total cholesterol（TC）,fasting plasma glucose（FPG） and fasting insulin（FINS） were measured.Apo CIII overexpression caused severe hypertriglyceridemia,but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups.The 4 groups of offspring had similar birth weight and growth rate.The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice,but there was no difference in plasma TG between maternal and paternal transgenic offspring.Although the FPG of the 4 groups of animals had no difference,the maternal transgenic mice showed impaired glucose tolerance,increased FINS levels and higher homeostasis model assessment insulin resistance index（HOMA-IR） than the other 3 groups.In conclusion,maternally inherited hypertriglyceridemia in Apo CIII transgenic mice displayed impaired glucose tolerance,hyperinsulinemia and increased HOMA-R,while paternally inherited hypertriglyceridemia did not have such impacts.

Development of a hamster model of spontaneous hypertriglyceridemia in diabetes

Hypertriglyceridemia(HTG)often accompanies diabetes and is considered a risk factor for diabetic vascular complications.However,inducing diabetic HTG typically requires high-fat diets in certain animal models.Leveraging our newly developed LDL receptor knockout hamster model,which exhibits features akin to human lipid metabolism,we sought to determine whether these animals would develop HTG without dietary manipulations in diabetes.Diabetes was induced via intraperitoneal injection of STZ in wild type and heterozygous LDL receptor deficient hamsters.Blood glucose,triglyceride,and cholesterol were measured over 60 days.Plasma TG clearance was determined via olive oil gavage.The effect of insulin on diabetic HTG was assessed on Day 60 post-diabetes induction.Blood glucose increased over threefold,while plasma insulin decreased to 30%of controls after STZ injection in both wild type and heterozygous hamsters by Day 7,remaining stable for 60 days.Plasma TG in wild-type hamsters remained unchanged at Day 7 post-STZ injection but increased slightly thereafter.Conversely,heterozygous hamsters exhibited severe HTG by Day 7 until the end of the study.Olive oil gavage revealed much slower plasma triglyceride clearance in heterozygous hamsters compared to WT animals,despite significantly reduced lipoprotein lipase activity in post-heparin plasma in both animals.Hyperglycemia and HTG in heterozygous hamsters were reversed to pre-diabetic levels following intraperitoneal insulin administration.In conclusion,severe HTG in diabetic heterozygous LDL receptor deficient hamsters developed spontaneously and was insulin-dependent.Thus,this hamster model holds promise for effectively studying the complications associated with human diabetic HTG.