Malprogramming of Hepatic Lipid Metabolism due to Excessive Early Cholesterol Exposure in Adult Progeny

Abstract

Scope The programming of hepatic lipid dysfunction in response to early cholesterol exposure and the influencing effects of postnatal diet was evaluated in apoE−/− mice. Methods and Results In two separate studies, female mice were assigned to a standard chow (S) or a cholesterol-enriched chow (C) diet during gestation and lactation. Male offspring from each dam were weaned on a postnatal S or a hypercaloric western (W) diet resulting in four experimental groups: S-S and C-S (Experiment 1) and S-W and C-W (Experiment 2). At weaning, litters from hypercholesterolemic mothers weighed less (p<0.05) and pups had higher blood lipids, glucose, and hepatic cholesterol compared with pups from S-fed mothers. Adult C-S offspring demonstrated an atherogenic lipid profile and increased (p<0.05) hepatic cholesterol and triglyceride content with altered lipid regulatory mRNA expression and protein content compared with S-S offspring. Alternatively, no difference (p>0.05) was observed between S-W and C-W in serum and hepatic lipid profiles, however, serum AST and ALT was higher (p<0.05) in C-W vs. S-W offspring. Conclusion The degree of hepatic lipid deposition observed in adult offspring exposed to excessive early cholesterol is influenced by the postnatal diet.

Excessive early-life cholesterol exposure may have later-life consequences for nonalcoholic fatty liver disease

“…In support of these findings, we have recently shown that MHC during the gestation period is associated with hepatic TG accumulation in fetal apoE −/− mice 80 which is similarly linked to a reduction in hepatic lipogenic mRNA expression. This response was similar to what we observed in newly weaned and adult males exposed to MHC throughout gestation and lactation described earlier 74,76 ( Table 2), suggesting that the programming of hepatic dysfunction in adulthood may originate in utero.…”

“…However, we have recently assessed the programming effects of MHC on hepatic lipid phenotype in adulthood and examined if the postnatal diet modulates these responses. 76 Male apoE −/− mice offspring from control or hypercholesterolemic mothers were weaned onto either a postnatal chow (3.5 kcal/g; 19.9% energy (E) from fat, 58.7% E from carbohydrate, 21.4% E from protein) or a Western diet (4.5 kcal/g; 40% E from fat, 44% E from carbohydrate, 15.8% E from protein) until 12 weeks of age. Adult offspring from MHC mothers fed the postnatal chow diet had increased hepatic TG which was characterized by a decreased hepatic SREBP1c, ACC, and FAS mRNA, indicative of reduced de novo lipogenesis and possibly a negative feedback mechanism in response to increased lipid stores.…”

Chronic Variable Stress Induces Hepatic Fe(II) Deposition by Up-Regulating ZIP14 Expression via miR-181 Family Pathway in Rats

“…High levels of AST and ALP are considered to be important markers of hepatotoxicity, as they are released into the extracellular fluid by the damaged liver [42,43]. High levels of AST and/or ALP have been reported to be induced by multiple stress responses, suggesting that the liver is a primary target of stress-induced damage.…”

“…For example, exposure of rats to acute cold-restraint stress significantly enhances serum AST levels [44]. In addition, both restraint stress and CCl 4 administration induce significant hepatic damage in rats, as identified by increased activities of serum AST and ALP [42,45]. Stress induction via immobilization also leads to the development of a significant enhancement in the activity of plasma AST [46].…”

Клінічна Характеристика Неалкогольної Жирової Хвороби Печінки У Вагітних На Тлі Ожиріння Різного Ступеня

“…В останні десятиліття епідемія ожиріння вразила жінок репродуктивного віку, оскільки спостерігається у більш ніж третини пацієнток у віці 20-40 років [1,2]. У процесі численних досліджень було виявлено, що у пацієнтів з абдомінальним ожирінням (від 20 до 30 % випадків) виявляють порушення функції печінки у вигляді різних форм НАЖХП [3][4][5][6][7]. У 25 % вагітних із НАЖХП розвивається неалкогольний стеатогепатит (НАСГ) на основі підвищення печінкових трансаміназ без ідентифікованих причин пошкодження гепатоцитів [8][9][10].…”