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D-galactose-induced aging aggravates obesity-induced bone dyshomeostasis.

ABSTRACT: We aimed to compare the time-course effect of D-galactose (D-gal)-induced aging, obesity, and their combined effects on bone homeostasis. Male Wistar rats were fed with either a normal diet (ND; n = 24) or a high-fat diet (HFD; n = 24) for 12 weeks. All rats were then injected with either vehicle or 150 mg/kg/day of D-gal for 4 or 8 weeks. Blood was collected to measure metabolic, aging, oxidative stress, and bone turnover parameters. Bone oxidative stress and inflammatory markers, as well as bone histomorphometry were also evaluated. Additionally, RAW 264.7 cells were incubated with either D-gal, insulin, or D-gal plus insulin to identify osteoclast differentiation capacity under the stimulation of receptor activator of nuclear factor κB ligand. At week 4, D-gal-induced aging significantly elevated serum malondialdehyde level and decreased trabecular thickness in ND- and HFD-fed rats, when compared to the control group. At week 8, D-gal-induced aging further elevated advanced glycation end products, increased bone inflammation and resorption, and significantly impaired bone microarchitecture in HFD-fed rats. The osteoclast number in vitro were increased in the D-gal, insulin, and combined groups to a similar extent. These findings suggest that aging aggravates bone dyshomeostasis in the obese condition in a time-dependent manner.

SUBMITTER: Imerb N

PROVIDER: S-EPMC9123171 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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D-galactose-induced aging aggravates obesity-induced bone dyshomeostasis.

Imerb Napatsorn N Thonusin Chanisa C Pratchayasakul Wasana W Arunsak Busarin B Nawara Wichwara W Ongnok Benjamin B Aeimlapa Ratchaneevan R Charoenphandhu Narattaphol N Chattipakorn Nipon N Chattipakorn Siriporn C SC

Scientific reports 20220520 1

We aimed to compare the time-course effect of D-galactose (D-gal)-induced aging, obesity, and their combined effects on bone homeostasis. Male Wistar rats were fed with either a normal diet (ND; n = 24) or a high-fat diet (HFD; n = 24) for 12 weeks. All rats were then injected with either vehicle or 150 mg/kg/day of D-gal for 4 or 8 weeks. Blood was collected to measure metabolic, aging, oxidative stress, and bone turnover parameters. Bone oxidative stress and inflammatory markers, as well as bo ...[more]

PMID: 35595806

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Project description:Fat-mass and obesity-associated protein (Fto) is highly expressed in the brain including, the hippocampus, and its expression is significantly decreased in the brain of Alzheimer's disease patients. In the present study, we measured Fto immunoreactivity and protein levels in the hippocampus of obese and aged mice, which were induced by high-fat diet for 12 weeks and D-galactose treatment for 10 weeks, respectively. The obesity and aging phenotypes were assessed by physiological parameters and Morris water maze test, respectively. High fat diet fed mice showed significant increases in body weight and blood glucose levels compared to that in the control or D-galactose-induced aged mice. In addition, treatment with D-galactose significantly decreased the spatial memory. Fto immunoreactivity in the control group was mainly detected in the pyramidal cells of the CA1 and CA3 regions and in the granule cells of the dentate gyrus. In the hippocampus of high-fat diet-fed mice, Fto immunoreactive structures were similarly found in the hippocampus compared to that in the control group, but Fto immunoreactivity in high-fat diet-fed mice was also found in the stratum oriens and radiatum of the CA1 and CA3 regions and the polymorphic layer of the dentate gyrus. In the hippocampus of D-galactose-induced aged mice, fewer Fto immunoreactive structures were detected in the granule cell layer of the dentate gyrus compared to the control group. Fto mRNA and protein levels based on quantitative real-time polymerase chain reaction and western blot assays were slightly increased in the hippocampus of high-fat diet-fed mice compared to that in control mice. In addition, Fto mRNA and protein levels were significantly decreased in the aged hippocampus compared to that in the control group. Fto protein levels are susceptible to the aging process, but not in the hippocampus of high-fat diet-induced obesity. The reduction of Fto in aged mice may be associated with reduced memory impairment in mice.

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Dataset Information

D-galactose-induced aging aggravates obesity-induced bone dyshomeostasis.

Publications

D-galactose-induced aging aggravates obesity-induced bone dyshomeostasis.

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