title: Lower hepatic iron storage associated with obesity in mice can be restored by decreasing body fat mass through feeding a low-fat diet.
abstract: High-fat diet (HFD)-induced obesity has been reported to result in low hepatic iron storage. In the current study, we tested the hypothesis that these obesity-related changes in hepatic iron status could be reversed by decreasing adiposity by feeding a low-fat diet. Five-week-old C57BL/6 mice were assigned to 3 groups: the LL group was fed a control diet for 31 weeks, the HH group was fed a HFD for 31 weeks, and the HL group was fed the HFD for 15 weeks and then switched to the control diet for 16 weeks. The fat mass of the HL group decreased by 3.2 g from the 14th to the 30th weeks. Fat mass was significantly different among the groups (11.4, 15.8, and 37.5 g in the LL, HH, and HL groups, respectively; P< .001). The liver iron concentration of the HL group was similar to that of the LL group, which was about 30% higher than that of the HH group (74.2, 72.7, and 55.7 μg/g in the LL, HL, and HH groups, respectively; P< .05). Duodenal cytochrome b messenger RNA (mRNA) levels were higher in the HL group than in the HH group. Although bone morphogenetic protein 6 (Bmp6) mRNA levels showed no significant differences in the liver, duodenal Bmp6 mRNA levels were significantly lower in the HH group compared with the LL and HL groups. Liver Smad1/5 proteins were differentially activated: the HH group had significantly less phosphorylated Smads than did the LL and HL groups. Our data demonstrate that hepatic iron storage levels are closely related to body adiposity, and reducing body fat mass through feeding a lower-fat diet to HFD-induced obese mice restores liver iron storage.
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea.
authors.forename: Hak
authors.initials: H
authors.lastname: Chung
authors.affiliation: JM USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wu
authors.affiliation: JM USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Donald
authors.initials: D
authors.lastname: Smith
authors.affiliation: JM USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA.
authors.forename: Simin Nikbin
authors.initials: SN
authors.lastname: Meydani
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Seoul National University, Seoul, Korea; Research Institute of Human Ecology, College of Human Ecology, Seoul National University, Seoul, Korea. Electronic address: snhan@snu.ac.kr.
authors.forename: Sung Nim
authors.initials: SN
authors.lastname: Han
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D050154:Adiposity; D000818:Animals; D055418:Bone Morphogenetic Protein 6 / Q000378:metabolism; D045303:Cytochromes b / Q000378:metabolism; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000008:administration & dosage* / Q000009:adverse effects; D004386:Duodenum / Q000378:metabolism; D005247:Feeding Behavior; D005260:Female; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000178:diet therapy* / Q000209:etiology / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051898:Smad1 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism
chemical_list: C525817:Bmp6 protein, mouse; D055418:Bone Morphogenetic Protein 6; D004041:Dietary Fats; D012333:RNA, Messenger; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D051902:Smad5 Protein; C497798:Smad5 protein, mouse; D045303:Cytochromes b; D007501:Iron
keywords: Diet modulation; Fat loss; Iron status; Mouse; Obesity