Perinatal, Metabolic and Reproductive Features in PPARG -related Lipodystrophy

Camille Gosseaume (1, 2) , Thierry Fournier (3) , Isabelle Jéru (1, 2, 4) , Marie-Léone Vignaud (3) , Isabelle Missotte (5) , Françoise Archambeaud (6) , Xavier Debussche (7) , Céline Droumaguet (8) , Bruno Fève (1, 2, 4, 4) , Sophie Grillot (9) , Bruno Guerci (10) , Sylvie Hieronimus (11) , Yves Horsmans , Estelle Nobécourt (7) , Catherine Pienkowski , Christine Poitou (12) , Jean-Paul Thissen , Olivier Lascols (1, 2, 4) , Séverine Degrelle (3) , Vassilis Tsatsaris (3) , Corinne Vigouroux (4, 1, 4, 2, 4) , Camille Vatier (4, 2)

1 CRSA - Centre de Recherche Saint-Antoine
2 IHU ICAN - Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière]
3 3PHM - UMR-S 1139 - Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal
4 CHU Saint-Antoine [AP-HP]
5 Centre hospitalier territorial Gaston-Bourret [Nouméa]
6 CHU Limoges
7 CHU La Réunion - Centre Hospitalier Universitaire de La Réunion
8 CHU Henri Mondor [Créteil]
9 Hôpitaux du Pays du Mont-Blanc
10 Hôpital Brabois
11 CHU Nice - Centre Hospitalier Universitaire de Nice
12 CHU Pitié-Salpêtrière [AP-HP]

Abstract 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.

Domains: Life Sciences [q-bio]

Camille Gosseaume, Thierry Fournier, Isabelle Jéru, Marie-Léone Vignaud, Isabelle Missotte, et al.. Perinatal, Metabolic and Reproductive Features in PPARG -related Lipodystrophy. European Journal of Endocrinology, 2023, 188 (3), pp.273-281. ⟨10.1093/ejendo/lvad023⟩. ⟨hal-04006255⟩