Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis

Abstract

Obesity is a risk factor for osteoarthritis (OA). To investigate the roles of increased mechanical loading in the onset of obesity-induced OA, knee joints were histologically analyzed after applying a tail suspension (TS) model to a high-fat diet (HFD)-induced OA model. Mice were divided into four groups: normal diet (ND) with normal loading (NL) group; HFD with NL group; ND with TS group; and HFD with TS group. Whole knee joints were evaluated by immunohistological analysis. The infrapatellar fat pad (IPFP) was excised and mRNA expression profiles were compared by qPCR analysis. After twelve weeks of the diet, body weight was increased by HFD in both the NL group and TS group. Upon histological analysis, the irregularity of the surface layer of articular cartilage was observed only in the NL+HFD group. Osteophyte area increased as a result of HFD in both the NL and TS groups, although osteophyte area in the TS+HFD group was smaller than that of the NL+HFD group. In the evaluation of the IPFP by qPCR, adipokines and inflammatory cytokines also increased as a result of HFD. While TGF-β increased as a result of HFD, the trend was slightly lower in the TS group, in parallel with osteophyte area. To detect apoptosis of articular chondrocytes, TUNEL staining was employed. TUNEL-positive cells were abundantly observed in the articular cartilage in the HFD mice regardless of mechanical loading. IPFP inflammation, enhanced chondrocyte apoptosis, and osteophyte formation were seen even in the TS group as a result of a HFD. In all, these data demonstrate that HFD contributed to osteophyte formation through mechanical loading dependent and independent mechanisms.

Phenotypic instability of chondrocytes in osteoarthritis: on a path to hypertrophy

“…Obesity, which is among the main risk factors for the development of OA, also contributes to the inflammatory environment in patients with OA. Obesity increases the risk of developing OA via load‐dependent and ‐independent mechanisms, as reflected in mouse models of high‐fat diet‐induced obesity . The adipose tissue acts as an endocrine organ that produces metabolites known as adipokines that contribute to systemic alterations in obese patients and can impact cartilage and bone in patients with OA.…”

“…Obesity increases the risk of developing OA via load-dependent and -independent mechanisms, 70,71 as reflected in mouse models of high-fat diet-induced obesity. 72 The adipose tissue acts as an endocrine organ that produces metabolites known as adipokines that contribute to systemic alterations in obese patients and can impact cartilage 70,71 and bone 73 in patients with OA. A number of studies have linked circulating or local adipokine levels to OA pathology, 66,70,74 including changes in serum resistin and visfatin levels in patients with hand OA.…”

Post-weaning high-fat diet results in growth cartilage lesions in young male rats

“…In contrast to previous studies which employed HF diets with fat content ranging from 30–62% to induce metabolic osteoarthritis, we detected no morphological evidence of changes consistent with early osteoarthritis on careful examination of large numbers of sections in any of the four groups [ 16 , 17 , 29 – 34 ]. Previous studies have introduced a HF diet at 8–12 weeks of age compared to 3 weeks of age in this study, and maintained animals on the HF diet for longer periods (commonly for at least 12 weeks), and may be why we did not observe any changes consistent with OA [ 29 – 31 , 35 ]. Further, the absence of OA lesions may also be because the rats were male (less active than females), and the obese and chronic inflammatory state induced was mild.…”

CITED2 mediates the mechanical loading–induced suppression of adipokines in the infrapatellar fat pad

“…The present study investigated whether the diminished expression of CITED2 would compromise the ability of an exercise regimen to modulate adipokine expression in the IPFP in Cited2 haploinsufficient mice subjected to an HFD. 36 We also examined changes in the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1␣, also known as PPARGC1A). It has recently been reported that PGC-1␣ is modulated by CITED2 in the regulation of hepatic gluconeogenesis.…”