De novo lipogenesis is an energy-expensive process whose role in adult mammals is poorly understood. We generated mice with liver-specific inactivation of fatty-acid synthase (FAS), a key lipogenic enzyme. On a zero-fat diet, FASKOL (FAS knockout in liver) mice developed hypoglycemia and fatty liver, which were reversed with dietary fat. These phenotypes were also observed after prolonged fasting, similarly to fasted PPARalpha-deficiency mice. Hypoglycemia, fatty liver, and defects in expression of PPARalpha target genes in FASKOL mice were corrected with a PPARalpha agonist. On either zero-fat or chow diet, FASKOL mice had low serum and hepatic cholesterol levels with elevated SREBP-2, decreased HMG-CoA reductase expression, and decreased cholesterol biosynthesis; these were also corrected with a PPARalpha agonist. These results suggest that products of the FAS reaction regulate glucose, lipid, and cholesterol metabolism by serving as endogenous activators of distinct physiological pools of PPARalpha in adult liver.

The prevention and treatment of PCOS, particularly in those who are obese, are essential in Chinese women of reproductive age.

Central nervous system control of energy balance affects susceptibility to obesity and diabetes, but how fatty acids, malonyl-CoA, and other metabolites act at this site to alter metabolism is poorly understood. Pharmacological inhibition of fatty acid synthase (FAS), rate limiting for de novo lipogenesis, decreases appetite independently of leptin but also promotes weight loss through activities unrelated to FAS inhibition. Here we report that the conditional genetic inactivation of FAS in pancreatic β cells and hypothalamus produced lean, hypophagic mice with increased physical activity and impaired hypothalamic PPARα signaling. Administration of a PPARα agonist into the hypothalamus increased PPARα target genes and normalized food intake. Inactivation of β cell FAS enzyme activity had no effect on islet function in culture or in vivo. These results suggest a critical role for brain FAS in the regulation of not only feeding, but also physical activity, effects that appear to be mediated through the provision of ligands generated by FAS to PPARα. Thus, 2 diametrically opposed proteins, FAS (induced by feeding) and PPARα (induced by starvation), unexpectedly form an integrative sensory module in the central nervous system to orchestrate energy balance. IntroductionHigher organisms adapt to changes in energy needs by assimilating peripheral hormonal and nutritional cues and integrating them in the central nervous system (1, 2). Even subtle defects in this system have deleterious consequences since modest excess weight in humans is associated with increased mortality (3, 4). The most thermodynamically efficient strategy for weight loss is appetite suppression, a difficult goal given the diversity of factors regulating food intake, ranging from amines and peptides to metabolites and fatty acids (reviewed in ref. 5).Fatty acid metabolism affects feeding behavior. Malonyl-CoA, an intermediary substrate controlling fatty acid flux, and carnitine palmitoyltransferase-1 (CPT-1), which allows fatty acids access to mitochondria for β-oxidation, have been independently implicated in regulating appetite (6, 7). Pharmacological inhibition of fatty acid synthase (FAS), the multifunctional enzyme that utilizes malonyl-CoA for the first committed step in fatty acid biosynthesis (8), with the compound C75 produces anorexia and weight loss in mice in the setting of increased malonyl-CoA (9). However, recent studies indicate that these effects on malonyl-CoA alone may not be sufficient to induce anorexia, as C75 also has an impact on the sympathetic nervous system and metabolic mediators, including PPARα and PPARγ coactivator-1 α (PGC1α) (10, 11). In addition,

In China, 25% of couples actively attempting to become pregnant suffered infertility.

This study was carried out to explore associations between assisted reproductive technology (ART) and maternal and neonatal outcomes compared with similar outcomes following spontaneously conceived births. We conducted a retrospective cohort study of pregnancies conceived by ART (N = 2641) during 2006–2014 compared to naturally conceived pregnancies (N = 5282) after matching for maternal age and birth year. Pregnancy complications, perinatal complications and neonatal outcomes of enrolled subjects were investigated and analysed by multivariate logistic regression. We found that pregnancies conceived by in vitro fertilization (IVF) were associated with a significantly increased incidence of gestational diabetes mellitus, gestational hypertension, preeclampsia, intrahepatic cholestasis of pregnancy, placenta previa, placental abruption, preterm premature rupture of membranes, placental adherence, postpartum haemorrhage, polyhydramnios, preterm labour, low birth weight, and small-for-date infant compared with spontaneously conceived births. Pregnancies conceived by intracytoplasmic sperm injection (ICSI) showed similar elevated complications, except some of the difference narrowed or disappeared. Singleton pregnancies or nulliparous pregnancies following ART still exhibited increased maternal and neonatal complications. Therefore, we conclude that pregnancies conceived following ART are at increased risks of antenatal complications, perinatal complications and poor neonatal outcomes, which may result from not only a higher incidence of multiple pregnancy, but also the manipulation involved in ART processes.