Objective To investigate the effects of manganese supplementation on the obesity induced by high-fat diet in mice. Methods Forty-eight male C57BL/6 mice were randomly divided into four groups: control group (control), manganese group (Mn), high-fat diet group (HFD), and HFD plus manganese supplementation group (HFD+Mn), with 12 mice in each group. Groups HFD and HFD+Mn were fed a high-fat diet (60% fat, 20% protein and 20% carbohydrate) for 12 weeks, and the other two groups were fed a control diet (10% fat, 20% protein and 70% carbohydrate). The Mn and the HFD+Mn groups were received 1.43 mg/kg Mn orally during the feeding period. Body weight and body composition were detected. After 12 weeks, the mice were anesthesized and specimens were collected. The contents of manganese in blood and biochemical markers in serum were examined. The pathological change of brown adipose tissue (BAT) was observed. The oxidative stress were evaluated in brown adipose tissue (BAT) by analyzing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). The effects of Mn supplementation and HFD on BAT mitochondrial function were assessed by detecting the mitochondrial ROS (mtROS), ATP level and mitochondrial membrane potential. Results Compared to the control group, body weight, fat mass, and serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) of the HFD group were notably elevated (P<0.05), while the level of high-density lipoprotein cholesterol (HDL-C) significantly reduced (P<0.05). HE staining revealed that the morphology of BAT was abnormal in the HFD group. The oxidative stress in BAT was obviously increased, manifested as increased contents of ROS and MDA. Increase of mitochondrial ROS (mtROS), and decrease of ATP level and mitochondrial membrane potential were also observed in BAT (P<0.05). Mn supplementation reduced the degree of obesity in mice (P<0.05), improved serum lipid levels (P<0.05), and alleviated the abnormal morphology of BAT. Mn supplementation also decreased oxidative stress and improved mitochondrial function in BAT (P<0.05). Conclusion Mn supplementation can ameliorate obesity induced by high-fat diet and improve mitochondrial function of BAT in mice.
Key words
obesity /
manganese /
brown adipose tissue /
mitochondrial function /
mice
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References
[1] Wang Y, Zhao L, Gao L, et al. Health policy and public health implications of obesity in China[J]. Lancet Diabetes Endocrinol, 2021, 9: 446–461.
[2] Chen L, Lei Y, Lu C, et al. Punicic acid ameliorates obesity-related hyperlipidemia and fatty liver in mice via regulation of intestinal flora and lipopolysaccharide-related signaling pathways[J]. Food Funct, 2024, 15: 5012–5025.
[3] Al-Raddadi R, Bahijri SM, Jambi HA, et al. The prevalence of obesity and overweight, associated demographic and lifestyle factors, and health status in the adult population of Jeddah, Saudi Arabia[J]. Ther Adv Chronic Dis, 2019, 10: 1–10.
[4] Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and cardiovascular disease: a scientific statement from the American Heart Association[J]. Circulation, 2021, 143: e984–e1010.
[5] García-Miranda A, Garcia-Hernandez A, Castañeda-Saucedo E, et al. Adipokines as regulators of autophagy in obesity-linked cancer[J]. Cells, 2022, 11:3230–3253.
[6] Wang S, He T, Luo Y, et al. SOX4 facilitates brown fat development and maintenance through EBF2-mediated thermogenic gene program in mice[J]. Cell Death Differ, 2025, 32: 447–465.
[7] Gonzalez-Hurtado E, Lee J, Choi J, et al. Fatty acid oxidation is required for active and quiescent brown adipose tissue maintenance and thermogenic programing[J]. Mol Metab, 2018, 7: 45–56.
[8] Harms M, Seale P.Brown and beige fat: development, function and therapeutic potential[J]. Nat Med, 2013, 19: 1252–1263.
[9] Jastroch M, Withers KW, Taudien S, et al. Marsupial uncoupling protein 1 sheds light on the evolution of mammalian nonshivering thermogenesis[J]. Physiol Genomics, 2008, 32: 161–169.
[10] Wang Y, Li J, Zhuang J, et al. Manganese in health and disease[J]. Nutr Res Rev, 2025, 38: 900–910.
[11] Aschner JL, Aschner M.Nutritional aspects of manganese homeostasis[J]. Mol Aspects Med, 2005, 26: 353–362.
[12] Kazi TG, Afridi HI, Kazi N, et al. Copper, chromium, manganese, iron, nickel, and zinc levels in biological samples of diabetes mellitus patients[J]. Biol Trace Elem Res, 2008, 122: 1–18.
[13] Volkov NF.Cobalt, manganses and zinc content in the blood of atherosclerosis patients[J]. Fed Proc Transl Suppl, 1963, 22: 897–899.
[14] Zhou B, Su X, Su D, et al. Dietary intake of manganese and the risk of the metabolic syndrome in a Chinese population[J]. Br J Nutr, 2016, 116: 853–863.
[15] Han X, Zhang B, Gong Q, et al. The tolerable upper intake level of manganese alleviates Parkinson-like motor performance and neuronal loss by activating mitophagy[J]. Free Radic Biol Med, 2024, 225: 665–676.
[16] Li L, Yang X.The essential element manganese, oxidative stress, and metabolic diseases: links and interactions[J]. Oxid Med Cell Longev, 2018, 2018: 7580707–7580717.
[17] Yang T, Wang X, Wen M, et al. Effect of manganese supplementation on the carcass traits, meat quality, intramuscular fat, and tissue manganese accumulation of Pekin duck[J]. Poult Sci, 2021, 100: 101064–101074.
[18] Wang J, Dong J, Zhong F, et al. Microbiome-metabolome analysis insight into the effects of the extract of Phyllanthus emblica L. on high-fat diet-induced hyperlipidemia[J]. Metabolites, 2024, 14: 257–275.
[19] Prasun P.Mitochondrial dysfunction in metabolic syndrome[J]. Biochim Biophys Acta Mol Basis Dis,2020, 1866:165838-165843.
[20] Abate M, Festa A, Falco M, et al. Mitochondria as playmakers of apoptosis, autophagy and senescence[J]. Semin Cell Dev Biol, 2020, 98: 139–153.