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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\u00a0% reduction in food intake. Contrary to our expectation, epididymal and carcass fat depots and adipocyte size were significantly enlarged by 15, 72 and 68\u00a0%, respectively, in the IF mice compared with the<jats:italic>ad libitum<\/jats:italic>-fed mice. Accordingly, plasma levels of leptin were 50\u00a0% higher in the IF mice than in the<jats:italic>ad libitum<\/jats:italic>-fed mice. In addition, the IF mice showed increased plasma levels of total cholesterol (37\u00a0%), VLDL-cholesterol (195\u00a0%) and LDL-cholesterol (50\u00a0%). 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\u00a0%), insulinaemia (50\u00a0%), glucose intolerance and insulin resistance were observed in the IF mice. Systemic inflammatory markers, TNF-\u03b1 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.<\/jats:p>","DOI":"10.1017\/s0007114513003383","type":"journal-article","created":{"date-parts":[[2013,11,1]],"date-time":"2013-11-01T13:27:00Z","timestamp":1383312420000},"page":"979-986","source":"Crossref","is-referenced-by-count":39,"title":["Food restriction by intermittent fasting induces diabetes and obesity and aggravates spontaneous atherosclerosis development in hypercholesterolaemic mice"],"prefix":"10.1017","volume":"111","author":[{"given":"Gabriel G.","family":"Dorighello","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana C.","family":"Rovani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J. 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