High‐fat diet‐induced obesity augments the deleterious effects of estrogen deficiency on bone: Evidence from ovariectomized mice

Abstract

Several epidemiological studies have suggested that obesity complicated with insulin resistance and type 2 diabetes exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high‐fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (10%fat) for 12 weeks. HFD‐OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD‐OVX, p < 0.0005) and impaired glucose tolerance. Bone microCT‐scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) (−15.6 ± 0.48% in HFD and −37.5 ± 0.235% in HFD‐OVX, p < 0.005) and expansion of bone marrow adipose tissue (BMAT; +60.7 ± 9.9% in HFD vs. +79.5 ± 5.86% in HFD‐OVX, p < 0.005). Mechanistically, HFD‐OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis, inflammation, downregulation of gene markers of bone formation and bone development. Similarly, HFD‐OVX treatment resulted in significant changes in bone tissue levels of purine/pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in postmenopausal women.

Association between fibrinogen and bone mineral density in postmenopausal women

“…This may be related to dietary habits and body fat distribution in different races, especially ectopic and visceral fat [ 9 ]. Some experimental animal studies have found that high-fat diet-induced obesity increases the deleterious effects of estrogen deficiency on bone in a mouse model of postmenopausal women, and that obesity and estrogen deficiency may affect inflammation levels leading to increased bone fragility [ 19 ]. The higher fat intake in the modern diet has led to a higher proportion of polyunsaturated fatty acids (PUFA), resulting in low-grade chronic inflammation (LGCI), which promotes the development of many chronic diseases, including obesity and osteoporosis [ 20 ].…”

Synergic Action of Systemic Risedronate and Local Rutherpy in Peri-implantar Repair of Ovariectomized Rats: Biomechanical and Molecular Analysis

“…The changes in body weight and Lee index of the animals can be explained by the association of the cafeteria diet (hyperlipidemic) with the depletion of estrogen levels resulting from the surgical procedure of ovariectomy, which mimicked the postmenopausal period in humans. During this period, in addition to the loss of the protective role of estrogen on the skeletal system, there is an increase in circulating androgens, leading to changes in body fat distribution that favor an accumulation of abdominal fat [8,[47][48][49]. It is worth mentioning that although the animals did not show large variations in their glycemia, insulin resistance is a very common factor observed in overweight or obese people, and if not controlled, can lead to consequences such as type 2 diabetes [18,20,50].…”

“…The postmenopausal period may also be associated with a change in the lifestyle of the population, which often becomes sedentary and involves poor dietary habits [7]. During this period, with the loss of the protective role of estrogen and the consequent increase in circulating androgens, the distribution of body fat may also change [8], leading to the development of abdominal obesity and metabolic syndrome [9][10][11].…”

Folic acid supplementation prevents high body fat-induced bone loss through TGR5 signaling pathways

“…Therefore, we speculated that folic acid intake may affect total BMD, thereby affecting bone health. The previous study found that body fat is closely related to bone health, 27,28 but it is still unclear whether the effect of folic acid on BMD is directly caused or mediated by body fat. Therefore, we analyzed the body fat rate as an intermediary factor of folic acid on BMD, and the mediating effect accounted for 82.7% of the total effect (Fig.…”