Peroxisome proliferator-activated receptor α (PPARα) has been reported to induce a potent anti-inflammatory response. Autophagy is a recently recognized rudimentary cellular response to inflammation and injury. The aim of the present study was to test the hypothesis that PPARα activation mediates autophagy to inhibit liver inflammation and protect against acute liver failure (ALF). PPARα expression during ALF and the impact of PPARα activation by Wy-14 643 on the hepatic immune response were studied in a D-galactosamine/lipopolysaccharide-induced mouse model. Autophagy was inhibited by 3-methyladenine or small interfering RNA (siRNA) against Atg7. In both the mouse model and human ALF subjects, PPARα was significantly downregulated in the injured liver. PPARα activation by pretreatment with Wy-14 643 protected against liver injury in mice. The protective effect of PPARα activation relied on the suppression of inflammatory mechanisms through the induction of autophagy. This hypothesis is supported by the following evidence: first, PPARα activation suppressed proinflammatory responses and inhibited phosphorylated NF-κBp65, phosphorylated JNK and phosphorylated ERK pathways in vivo. Second, protection by PPARα activation was due to the induction of autophagy because inhibition of autophagy by 3-methyladenine or Atg7 siRNA reversed liver protection and inflammation. Third, PPARα activation directly induced autophagy in primary macrophages in vitro, which protected cells from a lipopolysaccharide-induced proinflammatory response. Here, for the first time, we have demonstrated that PPARα-mediated induction of autophagy ameliorated liver injury in cases of ALF by attenuating inflammatory responses, indicating a potential therapeutic application for ALF treatment.

A carbohydrate-predominant LES is associated with increases in fasting carbohydrate oxidation, REE and reductions in fat oxidation in adults with ACLF. Therapeutic strategies utilizing LES may promote improved nutritional status in adults with ACLF.

ABSTRACT. This study explored the effects of levothyroxine (L-T4) replacement therapy on pregnancy outcomes in patients with subclinical hypothyroidism (SCH). We analyzed the effects on pregnancy outcomes with respect to gestational week when the desired thyroid-stimulating hormone (TSH) level was reached as well as the length of time required to reach the target level during L-T4 treatment. This study enrolled 457 patients diagnosed with SCH upon initial thyroid function screening. Subjects were assigned to the treatment group (N = 184), and the control group (N = 273). Two variables were analyzed in the treatment group: the gestational week when the target TSH level was achieved and the length of time required to reach the target level during treatment. Based on these criteria, the treatment group was further divided into subgroups, including three subgroups based on the time required to reach target levels (<4 weeks, 4-8 weeks, and >8 weeks) and gestational week when the target TSH level was achieved (before the 12th, between the 12th-28th, and after the 28th gestational week). The overall risk of complications in the control group was significantly higher than in the treatment group (P < 0.05). After L-T4 treatment, the incidences of premature rupture of fetal membranes (PROM), gestational diabetes mellitus, fetal macrosomia, and postpartum hemorrhage in the group with treatment duration <4 weeks were significantly lower than those in the groups with 4-8 and >8 weeks treatment duration (P < 0.05). L-T4 treatment can significantly reduce the risks of adverse pregnancy outcomes in pregnant women with SCH. The shorter the treatment duration required to reach the target TSH level and the earlier the gestational week when the target TSH level is achieved through treatment, the lower the incidence of complications.