Identification of blood cell transcriptome-based biomarkers in adulthood predictive of increased risk to develop metabolic disorders using early life intervention rat models

Autor: Brigitte M. Winklhofer-Roob, Gernot Faustmann, Teresa Priego, Johannes M. Roob, Jaap Keijer, Evert M. van Schothorst, Barbara Obermayer-Pietsch, Mariona Palou, Beate Tiran, Nara Szostaczuk, Melissa Bekkenkamp-Grovenstein, Catalina Picó, Juana Sánchez, Andreu Palou
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
Biochemistry
Transcriptome
predictive biomarkers
0302 clinical medicine
Pregnancy
Lactation
2. Zero hunger
Leptin
Gene Expression Regulation
Developmental
gestational calorie restriction
metabolic programing
medicine.anatomical_structure
Prenatal Exposure Delayed Effects
Human and Animal Physiology
Gestation
Biomarker (medicine)
Female
Biotechnology
medicine.medical_specialty
Offspring
Calorie restriction
Peripheral blood mononuclear cell
03 medical and health sciences
Metabolic Diseases
Internal medicine
Genetics
medicine
Animals
Rats
Wistar
Molecular Biology
Caloric Restriction
VLAG
metabolic health
business.industry
Rats
NPC1
Disease Models
Animal
030104 developmental biology
Endocrinology
PBMCs
Leukocytes
Mononuclear
WIAS
Fysiologie van Mens en Dier
business
030217 neurology & neurosurgery
Biomarkers
Zdroj: FASEB Journal, 34(7), 9003-9017
FASEB Journal 34 (2020) 7
ISSN: 0892-6638
9003-9017
DOI: 10.1096/fj.202000071rr
Popis: Calorie restriction during gestation in rats has long-lasting adverse effects in the offspring. It induces metabolic syndrome-related alterations, which are partially reversed by leptin supplementation during lactation. We employed these conditions to identify transcript-based nutrient sensitive biomarkers in peripheral blood mononuclear cells (PBMCs) predictive of later adverse metabolic health. The best candidate was validated in humans. Transcriptome analysis of PBMCs from adult male Wistar rats of three experimental groups was performed: offspring of control dams (CON), and offspring of 20% calorie-restricted dams during gestation without (CR) and with leptin supplementation throughout lactation (CR-LEP). The expression of 401 genes was affected by gestational calorie restriction and reversed by leptin. The changes preceded metabolic syndrome-related phenotypic alterations. Of these genes, Npc1 mRNA levels were lower in CR vs CON, and normalized to CON in CR-LEP. In humans, NPC1 mRNA levels in peripheral blood cells (PBCs) were decreased in subjects with mildly impaired metabolic health compared to healthy subjects. Therefore, a set of potential transcript-based biomarkers indicative of a predisposition to metabolic syndrome-related alterations were identified, including NPC1, which was validated in humans. Low NPC1 transcript levels in PBCs are a candidate biomarker of increased risk for impaired metabolic health in humans.
Databáze: OpenAIRE
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