Dysregulation of Placental Lipid Hydrolysis by High-Fat/High-Cholesterol Feeding and Gestational Diabetes Mellitus in Mice

• Published in: International journal of molecular sciences 2022-10, Vol.23 (20), p.12286
• Main Authors: Kuentzel, Katharina B, Bradić, Ivan, Mihalič, Zala N, Korbelius, Melanie, Rainer, Silvia, Pirchheim, Anita, Kargl, Julia, Kratky, Dagmar
• Format: Article
• Language: English
• Subjects: Accumulation; Animals; Body mass index; Cholesterol; Cholesterol Esters; Diabetes mellitus; Diabetes, Gestational; Enzymes; Esters; Exports; Fatty Acids; Female; fetal lipid accumulation; Fetal Macrosomia; Fetuses; Gene expression; Gestational diabetes; Glucose; Glycerol; Homeostasis; Humans; Hydrolysis; Intracellular; intracellular lipases; Lipase; Lipids; maternal high-fat diet; Metabolism; Metabolites; Mice; mouse placenta; Obesity; Obesity - complications; Overweight; Placenta; Pregnancy; Protein expression; Proteins; Risk analysis; Risk factors; Sterol Esterase; Triglycerides; Womens health
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232012286

Advanced maternal age and obesity are the main risk factors to develop gestational diabetes mellitus (GDM). Obesity is a consequence of the increased storage of triacylglycerol (TG). Cytosolic and lysosomal lipid hydrolases break down TG and cholesteryl esters (CE) to release fatty acids (FA), free cholesterol, and glycerol. We have recently shown that intracellular lipases are present and active in the mouse placenta and that deficiency of lysosomal acid lipase alters placental and fetal lipid homeostasis. To date, intracellular lipid hydrolysis in GDM has been poorly studied despite the important role of FA in this condition. Therefore, we hypothesized that intracellular lipases are dysregulated in pregnancies complicated by maternal high-fat/high-cholesterol (HF/HCD) feeding with and without GDM. Placentae of HF/HCD-fed mice with and without GDM were more efficient, indicating increased nutrient transfer to the fetus. The increased activity of placental CE but not TG hydrolases in placentae of dams fed HF/HCD with or without GDM resulted in upregulated cholesterol export to the fetus and placental TG accumulation. Our results indicate that HF/HCD-induced dysregulation of placental lipid hydrolysis contributes to fetal hepatic lipid accumulation and possibly to fetal overgrowth, at least in mice.