Anorexia nervosa (AN) in its two major types (restricting type and binge-eating/purging type) is one of the most frequent and serious eating disorder. Severe undernutrition due to intake restriction and pathological associated behaviors such as potomania and vomiting can cause serious somatic complications such as cardiac and/or hepatic disturbances. Nutritional rehabilitation of undernourished AN patients should be very causes to avoid refeeding syndrome. Managing AN need a multidisciplinary approach including psychiatric and nutritional care.
The transcription factor peroxisome proliferator‐activated receptor gamma (PPARG) is essential for placental development, and alterations in its expression and/or activity are associated with human placental pathologies such as pre‐eclampsia or IUGR. However, the molecular regulation of PPARG in cytotrophoblast differentiation and in the underlying mesenchyme remains poorly understood. Our main goal was to study the impact of mutations in the ligand‐binding domain (LBD) of the
PPARG
gene on cytotrophoblast fusion (PPARG
E352Q
) and on fibroblast cell migration (PPARG
R262G
/PPARG
L319X
). Our results showed that, compared to cells with reconstituted PPARG
WT
, transfection with PPARG
E352Q
led to significantly lower PPARG activity and lower restoration of trophoblast fusion. Likewise, compared to PPARG
WT
fibroblasts, PPARG
R262G
/PPARG
L319X
fibroblasts demonstrated significantly inhibited cell migration. In conclusion, we report that single missense or nonsense mutations in the LBD of PPARG significantly inhibit cell fusion and migration processes.
Objective
The adipogenic PPARG-encoded PPARγ nuclear receptor also display essential placental functions. We evaluated metabolic, reproductive and perinatal features of patients with PPARG-related lipodystrophy.
Methods
Current and retrospective data were collected in patients referred to a National Rare Diseases Reference Centre.
Results
26 patients from 15 unrelated families were studied (18 women, median age 43 years). They carried monoallelic PPARG variants except a homozygous patient with congenital generalized lipodystrophy. Among heterozygous patients aged 16 or more (n = 24), 92% had diabetes, 96% partial lipodystrophy (median age at diagnosis 24 and 37 years, respectively), 78% hypertriglyceridemia, 71% liver steatosis and 58% hypertension. Mean BMI was 26 ± 5.0 kg/m2. Women (n = 16) were frequently affected by acute pancreatitis (n = 6) and/or polycystic ovary syndrome (n = 12). Eleven women obtained one or several pregnancies, all complicated by diabetes (n = 8), hypertension (n = 4) and/or hypertriglyceridemia (n = 10). We analysed perinatal data of patients according to the presence (n = 8) or absence (n = 9) of maternal dysmetabolic environment. The median gestational age at birth was low in both groups (37 and 36 weeks of amenorrhea, respectively). As expected, birth weight was higher in patients exposed to a fetal dysmetabolic environment of maternal origin. In contrast, 85.7% of non-exposed patients, in whom the variant is, or is very likely to be, paternally-inherited, were small for gestational age.
Conclusions
Lipodystrophy-related PPARG variants induce early metabolic complications. Our results suggest that placental expression of PPARG pathogenic variants carried by affected fetuses could impair prenatal growth and parturition. This justifies careful pregnancy monitoring in affected families.
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