How high‐fat diet affects bone in mice: A systematic review and meta‐analysis

Abstract

High-fat diet (HFD) feeding for mice is commonly used to model obesity. However, conflicting results have been reported on the relationship between HFD and bone mass. In this systematic review and meta-analysis, we synthesized data from 80 articles to determine the alterations in cortical and trabecular bone mass of femur, tibia, and vertebrae in C57BL/6 mice after HFD. Overall, we detected decreased trabecular bone mass as well as deteriorated architecture, in femur and tibia of HFD treated mice. The vertebral trabecula was also impaired, possibly due to its reshaping into a more fragmentized pattern. In addition, pooled cortical thickness declined in femur, tibia, and vertebrae. Combined with changes in other cortical parameters, HFD could lead to a larger femoral bone marrow cavity, and a thinner and more fragile cortex.Moreover, we conducted subgroup analyses to explore the influence of mice's sex and age as well as HFD's ingredients and intervention period. Based on our data, male mice or mice aged 6-12 weeks old are relatively susceptible to HFD. HFD with > 50% of energy from fats and intervention time of 10 weeks to 5 months are more likely to induce skeletal alterations. Altogether, these findings supported HFD as an appropriate model for obesity-associated bone loss and can guide future studies.

Interaction between ferroptosis and TNF‐α: Impact in obesity‐related osteoporosis

“…It has been reported that estrogen level leads to critical differences in inflammation and bone mass of obese individuals. 10,87,88 Male mice display more pronounced inflammation with obviously elevated proinflammatory cytokines especially TNF-α and suffer more severe trabecular bone loss than females after a long-term high-fat diet. 10,89 Besides, there is a potential correlation between body weight and estrogen levels in females.…”

“…10,87,88 Male mice display more pronounced inflammation with obviously elevated proinflammatory cytokines especially TNF-α and suffer more severe trabecular bone loss than females after a long-term high-fat diet. 10,89 Besides, there is a potential correlation between body weight and estrogen levels in females. 90 Therefore, if females were used, estrogen level would be a profound factor affecting bone health and serum TNF-α levels in rats thus greatly increasing research difficulties.…”

“…Since obesity is specifically characterized by excess fat accumulation, recent clinical trials have investigated the correlation between fat mass or fat percentage and bone health, and considered fat accumulation as a negative modulator of bone characteristics 5–8 . Besides, the majority of obese rodents display a low bone mass and quality phenotype, which further challenges the traditional understanding that obesity exerts beneficial effects on bone health 9–11 . Of note, mechanical loading due to body weight has profound impacts on cortical and trabecular bone microarchitectures.…”

“…[5][6][7][8] Besides, the majority of obese rodents display a low bone mass and quality phenotype, which further challenges the traditional understanding that obesity exerts beneficial effects on bone health. [9][10][11] Of note, mechanical loading due to body weight has profound impacts on cortical and trabecular bone microarchitectures. Some trabecular and cortical bone parameters including trabecular number, trabecular thickness, trabecular separation, and cortical thickness could scale with body weight.…”

Sciadonic acid attenuates high-fat diet-induced bone metabolism disorders in mice

“…2,3 The metabolic syndrome is not merely a superimposition of multiple chronic conditions but an integrative state where such conditions act in a synergistic manner to produce deleterious systemic effects, including effects on bone homeostasis. 4 Bone tissue has multiple vital functions, such as support, protection, and hematopoiesis. Bone homeostasis is maintained by the balance of osteoblast and osteoclast activities, and breaking this balance will lead to a series of bone diseases.…”