The role of PPARγ in childhood obesity-induced fractures

Abstract

Globally, obesity is on the rise with ~ 30% of the world’s population now obese, and childhood obesity is following similar trends. Childhood obesity has been associated with numerous chronic conditions, including musculoskeletal disorders. This review highlights the effects of childhood adiposity on bone density by way of analyzing clinical studies and further describing two severe skeletal conditions, slipped capital femoral epiphysis and Blount’s disease. The latter half of this review discusses bone remodeling and cell types that mediate bone growth and strength, including key growth factors and transcription factors that help orchestrate this complex pathology. In particular, the transcriptional factor peroxisome proliferator-activated receptor gamma (PPARγ) is examined as it is a master regulator of adipocyte differentiation in mesenchymal stem cells (MSCs) that can also influence osteoblast populations. Obese individuals are known to have higher levels of PPARγ expression which contributes to their increased adipocyte numbers and decreased bone density. Modulating PPAR*gamma* signaling can have significant effects on adipogenesis, thereby directing MSCs down the osteoblastogenesis pathway and in turn increasing bone mineral density. Lastly, we explore the potential of PPARγ as a druggable target to decrease adiposity, increase bone density, and be a treatment for children with obesity-induced bone fractures.

Amidation-Modified Apelin-13 Regulates PPARγ and Perilipin to Inhibit Adipogenic Differentiation and Promote Lipolysis

“…According to their different structures, PPARs can be divided into three types α, β, and c. Among them, PPARc is mainly expressed in adipose tissue and the immune system, which has adipose tissue specificity, and can regulate the expression of lipid metabolism enzymes. It plays an important regulatory role in adipogenic differentiation [12]. Lipid droplet coating protein perilipin is an important protein that regulates lipolysis and plays an important role in lipolysis [13].…”

The role of mesenchymal stem cells in early programming of adipose tissue in the offspring of women with obesity

“…In this respect, it is important to note that obesity is a condition associated to a disturbed muscle and bone physiology, together with higher intramuscular fat deposition and osteoporosis. 88,89 This suggests that proper development of these tissues may also be disturbed in utero. Also, this raises the question of whether other stem cell lineages could be compromised: are ectodermal and endodermal lineages altered by maternal obesity?…”

“…Could this result in a decreased differentiation towards muscle, bone and cartrilage cells? In this respect, it is important to note that obesity is a condition associated to a disturbed muscle and bone physiology, together with higher intramuscular fat deposition and osteoporosis 88,89 . This suggests that proper development of these tissues may also be disturbed in utero.…”

Alterations in Lysosome Homeostasis in Lipid-Related Disorders: Impact on Metabolic Tissues and Immune Cells

“…Although, the data suggest that the ATX-LPA axis reduces PPAR-c function, the specific mechanisms by which it contributes to obesity remains to be elucidated (Jose and Kienesberger 2021). In contrast, it has been reported that obese individuals have higher PPAR-c mRNA levels, which contributes to an increase in the numbers of adipocytes (Vidal-Puig et al, 1997;McCann and Ratneswaran 2019). Interestingly, activation of PPAR-c induces an increase in the number of small and insulin-sensitive adipocytes and upregulates adiponectin, improving insulin sensitivity in the liver and muscle (Jakab et al, 2021).…”