Journal
HELIYON
Volume 4, Issue 9, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.heliyon.2018.e00830
Keywords
Physiology; Biochemistry; Microbiology
Categories
Funding
- National Natural Science Foundation of China [31630036, 81390350]
- Ministry of Science and Technology of China [2016YFA0500103]
- Chinese Academy of Sciences [XDA12010102, QYZDJ495 SSW-SMC008, ZDRW-ZS-2016-8, Y817X11141]
- Chinese Academy of Sciences (CAS Interdisciplinary Innovation Team)
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Continuous deficiency of leucine, a member of branched chain amino acids, is able to reduce obesity and improve insulin sensitivity in mice. Intermittent fasting has been shown to be effective in intervention of metabolic disorders including diabetes. However, it is unknown whether intermittent leucine deprivation can intervene in type 2 diabetes progression. We administered leucine-deprived food every other day in db/db mice, a type 2 diabetes model, for a total of eight weeks to investigate the interventional effect of intermittent leucine deprivation. Intermittent leucine deprivation significantly reduces hyperglycemia in db/db mice independent of body weight change, together with improvement in glucose tolerance and insulin sensitivity. The total area of pancreatic islets and fE3 cell number are increased by intermittent leucine deprivation, accompanied by elevated proliferation of fE3 cells. The expression level of Ngn3, a fE3 cell progenitor marker, is also increased by leucine-deleted diet. However, leucine deficiency engenders an increase in fat mass and a decrease in lean mass. Lipid accumulation in the liver is elevated and liver function is compromised by leucine deprivation. In addition, leucine deficiency alters the composition of gut microbiota. Leucine deprivation increases the genera of Bacteroides, Alloprevotella, Rikenellaceae while reduces Lachnospiraceae and these changes are correlated with fasting blood glucose levels of the mice. Collectively, our data demonstrated that intermittent leucine deprivation can intervene in the progression of type 2 diabetes in db/db mice. However, leucine deficiency reduces lean mass and aggravates hepatic steatosis in the mouse.
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