title: Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice.
abstract: Different regimens of food restriction have been associated with protection against obesity, diabetes and CVD. In the present study, we hypothesised that food restriction would bring benefits to atherosclerosis- and diabetes-prone hypercholesterolaemic LDL-receptor knockout mice. For this purpose, 2-month-old mice were submitted to an intermittent fasting (IF) regimen (fasting every other day) over a 3-month period, which resulted in an overall 20 % reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68 %, respectively, in the IF mice compared with the ad libitum-fed mice. Accordingly, plasma levels of leptin were 50 % higher in the IF mice than in the ad libitum-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37 %), VLDL-cholesterol (195 %) and LDL-cholesterol (50 %). As expected, in wild-type mice, the IF regimen decreased plasma cholesterol levels and epididymal fat mass. Glucose homeostasis was also disturbed by the IF regimen in LDL-receptor knockout mice. Elevated levels of glycaemia (40 %), insulinaemia (50 %), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-α and C-reactive protein, were significantly increased and spontaneous atherosclerosis development were markedly increased (3-fold) in the IF mice. In conclusion, the IF regimen induced obesity and diabetes and worsened the development of spontaneous atherosclerosis in LDL-receptor knockout mice. Although being efficient in a wild-type background, this type of food restriction is not beneficial in the context of genetic hypercholesterolaemia.
authors.affiliation: Department of Structural and Functional Biology, Institutional of Biology, State University of Campinas, Rua Monteiro Lobato, 255 Campinas, SP, CEP 13083-862, Brazil.
authors.forename: Gabriel G
authors.initials: GG
authors.lastname: Dorighello
authors.affiliation: Department of Structural and Functional Biology, Institutional of Biology, State University of Campinas, Rua Monteiro Lobato, 255 Campinas, SP, CEP 13083-862, Brazil.
authors.forename: Juliana C
authors.initials: JC
authors.lastname: Rovani
authors.affiliation: Department of Structural and Functional Biology, Institutional of Biology, State University of Campinas, Rua Monteiro Lobato, 255 Campinas, SP, CEP 13083-862, Brazil.
authors.forename: Christopher J F
authors.initials: CJ
authors.lastname: Luhman
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Paim
authors.affiliation: Department of Structural and Functional Biology, Institutional of Biology, State University of Campinas, Rua Monteiro Lobato, 255 Campinas, SP, CEP 13083-862, Brazil.
authors.forename: Helena F
authors.initials: HF
authors.lastname: Raposo
authors.affiliation: Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, Brazil.
authors.forename: Anibal E
authors.initials: AE
authors.lastname: Vercesi
authors.affiliation: Department of Structural and Functional Biology, Institutional of Biology, State University of Campinas, Rua Monteiro Lobato, 255 Campinas, SP, CEP 13083-862, Brazil.
authors.forename: Helena C F
authors.initials: HC
authors.lastname: Oliveira
mesh_terms: D017667:Adipocytes / Q000473:pathology; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology*; D001786:Blood Glucose / Q000032:analysis; D001823:Body Composition; D048429:Cell Size; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003920:Diabetes Mellitus / Q000209:etiology*; D004822:Epididymis; D005215:Fasting / Q000009:adverse effects*; D005508:Food Deprivation; D018149:Glucose Intolerance / Q000209:etiology; D006937:Hypercholesterolemia / Q000150:complications* / Q000235:genetics; D007249:Inflammation / Q000209:etiology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology*; D011973:Receptors, LDL / Q000172:deficiency
chemical_list: D001786:Blood Glucose; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D007328:Insulin; D011973:Receptors, LDL; D002784:Cholesterol