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Distinct iron homeostasis in C57BL/6 and Balb/c mouse strains.

ABSTRACT: C57BL/6 (BL6) and Balb/c mice exhibit prototypical Th1- and Th2-dominant immune predispositions, respectively. Iron is a proinflammatory metal ion; however, limited information is documented on the differences in iron homeostasis between BL6 and Balb/c strains. The objective of this study was to investigate the extent to which strain-level differences in these mice dictates the regulation of iron homeostasis during physiologic and inflammatory conditions. At basal levels, Balb/c mice displayed significantly higher levels of iron in systemic circulation and tissue compared to BL6 mice. Moreover, Balb/c mice had greater iron absorption as indicated by higher gene expressions of duodenal DcytB, DMT1, Fpn, SFT, and Heph. Similarly, hepatic Tf, TfR1, TfR2, and DMT1 expressions were augmented in Balb/c mice. Interestingly, there was no change in hepatic Hamp expression between the two strains, suggesting that the disparity in their maintenance of iron is independent of hepcidin. Additionally, the basal levels of intracellular labile iron pool in Balb/c intestinal epithelial cells, and bone marrow-derived macrophages and neutrophils, were higher compared to BL6 mice. When mice were challenged with lipopolysaccharide, the acute inflammatory response in BL6 mice was more pronounced than in Balb/c mice, as indicated by the more rapid development of hypoferremia and upregulation of serum IL-6 and TNF-? levels in BL6 mice. In conclusion, this study underscores that iron homeostasis is distinct between BL6 and Balb/c strains under both physiologic and inflammatory conditions.

SUBMITTER: Saha P

PROVIDER: S-EPMC7210116 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Distinct iron homeostasis in C57BL/6 and Balb/c mouse strains.

Saha Piu P Xiao Xia X Li Yaqi Y Golonka Rachel M RM Abokor Ahmed A AA Yeoh Beng San BS Vijay-Kumar Matam M

Physiological reports 20200501 9

C57BL/6 (BL6) and Balb/c mice exhibit prototypical Th1- and Th2-dominant immune predispositions, respectively. Iron is a proinflammatory metal ion; however, limited information is documented on the differences in iron homeostasis between BL6 and Balb/c strains. The objective of this study was to investigate the extent to which strain-level differences in these mice dictates the regulation of iron homeostasis during physiologic and inflammatory conditions. At basal levels, Balb/c mice displayed s ...[more]

PMID: 32385968

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Project description:BackgroundAdaptive thermogenesis is an iron-demanding pathway, significantly contributing to whole-body energy expenditure. However, the effects of iron-deficient diets on adaptive thermogenesis and obesity remain unknown.ObjectivesWe aimed to determine the impact of dietary iron deficiency on iron homeostasis in adipocytes, adaptive thermogenic capacity, and metabolic consequences in obesity.MethodsC57BL/6 male mice were assigned to either the iron-adequate (IA, 35 ppm) or the iron-deficient group (ID, 3 ppm) at weaning. Upon 8 wk of age, both IA and ID groups received an isocaloric high-fat diet (45% kcal from fat) for 10 wk, maintaining the same iron content. Mice (n = 8) were used to determine the iron status at the systemic and tissue levels and lipid metabolism and inflammatory signaling in adipose tissue. The same mice were used to evaluate cold tolerance (4°C) for 3 h. For assessing adaptive thermogenesis, mice (n = 5) received an intraperitoneal injection of β3-adrenoceptor agonist CL316243 (CL) for 5 d.ResultsCompared with the IA group, the ID group had nonanemic iron deficiency, lower serum ferritin (42.8%, P < 0.01), and greater weight gain (8.67%, P < 0.05) and insulin resistance (159%, P < 0.01), partly due to reduced AMP-activated protein kinase activation (61.0%, P < 0.05). Upon cold exposure, the ID group maintained a core body temperature 2°C lower than the IA group. The ID group had lower iron content (47.0%, P < 0.01) in the inguinal adipose tissue (iWAT) than the IA group, which was associated with impaired adaptive thermogenesis. In response to CL, ID mice showed decreased heat production (P < 0.01) and defective upregulation of beige adipocyte-specific markers, including uncoupling protein 1 (41.1%, P < 0.001), transferrin receptor 1 (47.5%, P < 0.001), and mitochondrial respiratory chain complexes (P < 0.05) compared with IA mice.ConclusionsDietary iron deficiency deregulates iron balance in the iWAT and impairs adaptive thermogenesis, thereby escalating the diet-induced weight gain in C57BL/6 mice.

Project description:Pregnancy and lactation are characterized by dramatic changes in the endocrine system and brain in mammalian females. These changes, with stress before pregnancy, are potential risk factors for the development of postpartum depression (PPD). A valid animal model of PPD is needed to understand the neurobiological basis of the depressive state of females. To explore a mouse model of PPD, we first assessed anxiety-like and depression-related behaviors in nulliparous (virgin), nonlactating primiparous, and lactating primiparous females in four inbred strains of mice (C57BL/6J, C57BL/6JJcl, BALB/cAnNCrlCrlj, and BALB/cAJcl). Pups from the nonlactating female group were removed one day after parturition to examine the effects of physical interaction with pups on the postpartum behaviors. Second, we investigated the additional effects of prepregnancy stress (restraint stress for 6 h/day for 21 days) on postpartum behaviors in the BALB/cAJcl strain. We found that females of the two BALB/c substrains showed decreased locomotor activity and increased anxiety-like and depression-related behaviors compared with females of the two C57BL/6 substrains. Behavioral differences were also observed between the two substrains of each strain. Additionally, pregnancy- and lactation-dependent behavioral differences were found in some strains: lactating BALB/cAJcl females traveled shorter distance than the females of the other reproductive state groups, while nonlactating and lactating BALB/cAJcl and C57BL/6J females showed increased depression-related behavior compared with nulliparous females. Lactating BALB/cAJcl and C57BL/6JJcl females exhibited decreased sucrose preference or anhedonia-like behavior compared with nulliparous and nonlactating females, although these results did not reach statistical significance after correction for multiple testing. An additional independent experiment replicated the marked behavioral changes in lactating BALB/cAJcl females. Moreover, increased anxiety-like behavior was observed in lactating BALB/cAJcl females that experienced prepregnancy stress. These results suggest genetic contributions to the regulation of anxiety-like and depression-related behaviors in female mice. Furthermore, this study suggests that pregnancy and lactation cause decreased locomotor activity and increased depression-related behaviors, which was consistently found in our results, and that prepregnancy stress enhances anxiety-like behavior in the BALB/cAJcl strain. The inbred strain of female mice may be used as a potential model of PPD to further study the genetic and neurobiological mechanisms underlying the development of this disorder.

Dataset Information

Distinct iron homeostasis in C57BL/6 and Balb/c mouse strains.

Publications

Distinct iron homeostasis in C57BL/6 and Balb/c mouse strains.

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