Impact of apolipoprotein A1- or lecithin:cholesterol acyltransferase-deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice

Giuseppe Maulucci, Eva Xepapadaki, Caterina Constantinou, Eleni A. Karavia, Evangelia Zvintzou, Bareket Daniel, Shlomo Sasson, Kyriakos E. Kypreos

Risultato della ricerca: Contributo in rivistaArticolo in rivista

4 Citazioni (Scopus)

Abstract

High density lipoprotein (HDL) has attracted the attention of biomedical community due to its well-documented role in atheroprotection. HDL has also been recently implicated in the regulation of islets of Langerhans secretory function and in the etiology of peripheral insulin sensitivity. Indeed, data from numerous studies strongly indicate that the functions of pancreatic β-cells, skeletal muscles and adipose tissue could benefit from improved HDL functionality. To better understand how changes in HDL structure may affect diet-induced obesity and type 2 diabetes we aimed at investigating the impact of Apoa1 or Lcat deficiency, two key proteins of peripheral HDL metabolic pathway, on these pathological conditions in mouse models. We report that universal deletion of apoa1 or lcat expression in mice fed western-type diet results in increased sensitivity to body-weight gain compared to control C57BL/6 group. These changes in mouse genome correlate with discrete effects on white adipose tissue (WAT) metabolic activation and plasma glucose homeostasis. Apoa1-deficiency results in reduced WAT mitochondrial non-shivering thermogenesis. Lcat-deficiency causes a concerted reduction in both WAT oxidative phosphorylation and non-shivering thermogenesis, rendering lcat −/− mice the most sensitive to weight gain out of the three strains tested, followed by apoa1 −/− mice. Nevertheless, only apoa1 −/− mice show disturbed plasma glucose homeostasis due to dysfunctional glucose-stimulated insulin secretion in pancreatic β-islets and insulin resistant skeletal muscles. Our analyses show that both apoa1 −/− and lcat −/− mice fed high-fat diet have no measurable Apoa1 levels in their plasma, suggesting no direct involvement of Apoa1 in the observed phenotypic differences among groups.
Lingua originaleEnglish
pagine (da-a)1351-1360
Numero di pagine10
RivistaBIOCHIMICA ET BIOPHYSICA ACTA. MOLECULAR BASIS OF DISEASE
Volume1865
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • Adipose Tissue, White
  • Animals
  • Apolipoprotein A-I
  • Apolipoprotein A1
  • Diabetes
  • Diet, High-Fat
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Glucose
  • High density lipoprotein
  • Homeostasis
  • Insulin
  • Insulin Resistance
  • Islets of Langerhans
  • Lecithin Cholesterol Acyltransferase Deficiency
  • Lecithin-cholesterol acyltransferase
  • Lipoproteins, HDL
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria
  • Muscle, Skeletal
  • Obesity
  • Oxidative Phosphorylation
  • Pancreatic β-cells
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Signal Transduction
  • Skeletal muscle
  • Thermogenesis
  • Weight Gain

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