Obesity, but not high-fat diet, is associated with bone loss that is reversed via CD4+CD25+Foxp3+ Tregs-mediated gut microbiome of non-obese mice

Abstract

Osteoporosis is characterized by decreased bone mass, microarchitectural deterioration, and increased bone fragility. High-fat diet (HFD)-induced obesity also results in bone loss, which is associated with an imbalanced gut microbiome. However, whether HFD-induced obesity or HFD itself promotes osteoclastogenesis and consequent bone loss remains unclear. In this study, we developed HFD-induced obesity (HIO) and non-obesity (NO) mouse models to evaluate the effect of HFD on bone loss. NO mice were defined as body weight within 5% of higher or lower than that of chow diet fed mice after 10 weeks HFD feeding. NO was protected from HIO-induced bone loss by the RANKL /OPG system, with associated increases in the tibia tenacity, cortical bone mean density, bone volume of cancellous bone, and trabecular number. This led to increased bone strength and improved bone microstructure via the microbiome-short-chain fatty acids (SCFAs) regulation. Additionally, endogenous gut-SCFAs produced by the NO mice activated free fatty acid receptor 2 and inhibited histone deacetylases, resulting in the promotion of Treg cell proliferation in the HFD-fed NO mice; thereby, inhibiting osteoclastogenesis, which can be transplanted by fecal microbiome. Furthermore, T cells from NO mice retain differentiation of osteoclast precursors of RAW 264.7 macrophages ex vivo. Our data reveal that HFD is not a deleterious diet; however, the induction of obesity serves as a key trigger of bone loss that can be blocked by a NO mouse-specific gut microbiome.

Chromium nanoparticles improve bone turnover regulation in rats fed a high-fat, low-fibre diet

“…There are also reports that this type of diet affects the structure and health of the skeletal system, although opinions on the direction of this effect are clearly divided [25,26]. On the one hand, it has been suggested that excess adipose tissue deposited during intake of a high-fat diet, by increasing mechanical load, may stimulate bone-formation processes, leading to the achievement of peak bone mass and reducing the risk of osteoporosis [2,3].…”

“…The literature indicates that obesity, including obesity induced by chronic intake of a high-fat diet, may be accompanied by the development of numerous disorders, such as metabolic syndrome, insulin resistance, diabetes, cardiovascular disease, and even cancers [ 23 – 25 ]. There are also reports that this type of diet affects the structure and health of the skeletal system, although opinions on the direction of this effect are clearly divided [ 25 , 26 ]. On the one hand, it has been suggested that excess adipose tissue deposited during intake of a high-fat diet, by increasing mechanical load, may stimulate bone-formation processes, leading to the achievement of peak bone mass and reducing the risk of osteoporosis [ 2 , 3 ].…”

“…On the other hand, in recent years there have been increasing reports indicating that excessive consumption of an obesogenic Western diet adversely affects bone turnover, which negatively affects the functioning and structure ofbone tissue. In effect,the skeleton becomes more susceptible to micro damage and fractures [ 5 , 26 , 33 , 34 ]. Ionova-Martin et al [ 35 ] demonstrated that although obesity caused by a high-fat diet may be accompanied by increased bone tissue mass due to increased bone size and mineral content, its quality deteriorates as well (poorer mechanical properties).…”

“…susceptible to micro damage and fractures [5,26,33,34]. Ionova-Martin et al [35] demonstrated that although obesity caused by a high-fat diet may be accompanied by increased bone tissue mass due to increased bone size and mineral content, its quality deteriorates as well (poorer mechanical properties).…”