Early life high-fat diet and voluntary physical activity affect body composition, bone phenotype and gene expression in the male rat

Abstract

Background Childhood and adolescence are characterised by rapid musculoskeletal development and offer a window of opportunity for maximising skeletal gains through physical activity. Physical activity has also long been considered a non-pharmacological strategy to combat diet induced obesity and its associated co-morbidities. The classically accepted opinion that obesity has a protective effect on bone due to the increased mechanical demand imposed by the excessive body weight on the skeleton has been challenged in recent times. Animal models used to investigate the effects of physical activity on bone development often involve the use of forced exercise models. Such studies have the potential for data confounding as they elicit a stress response in the animals. A series of studies were conducted to undertand how voluntary physical activity and highfat diet affect the body composition, bone mass indices, bone and marrow transcriptome during early life using a male rat model. Firstly, two voluntary exercise modalities: bipedal stance (BPS) and wheel exercise (WEX), were evaluated for their ability to influence body composition and gene expression without eliciting a stress response during the prepubertal period. Next, gene expression changes in the diaphyseal bones of the exercised animals were determined. In the second study, we examined the effects of an early life high-fat diet on body composition, bone mass indices and marrow gene expression in a young adult male rat model. Next, the ability of voluntary physical activity to modulate the early life high-fat diet effects was evaluated. Finally, whether the bone marrow retains a memory of early life exercise following its cessation was investigated. There was a modality-dependent response to prepubertal physical activity. The WEX group had significantly greater lean mass percentage and lower fat mass percentage compared to the control (CON) group. In the femoral diaphysis, the cortical cross-sectional thickness and closed porosity of the WEX group was significantly greater than the CON group. Such differences were not observed in the BPS group with respect to either body composition or cortical bone parameters. This modality-specific response was also seen in the cortical bone gene expression. We observed that genes with functions in integrin-linked kinase (ILK) and calcium (Ca2+) signalling pathways, both prominent mechanotransduction pathways in bone, had a diametrically opposite response to wheel and bipedal stance exercises. Early life high-fat diet positively affected body weight, total fat percentage and bone mass indices. In the bone marrow, it resulted in adipocyte hypertrophy and a pro-inflammatory and pro-adipogenic gene expression profile. Crucially, the bone marrow of the rats that exercised using the wheel while on a high-fat diet retained a memory of the early life exercise even when the exercise was stopped for 60 days. In the bone marrow, the adipocyte size of the rats that exercised did not exhibit hypertrophy. Several genes associated with mature adipocyte function were downregulated in the early-exercise group. Moreover, response of adiponectin gene expression in the marrow was different to that documented in white adipose tissues indicating that the the marrow adipose tissue may have a unique response to high-fat feeding. These results show that short-term prepubertal voluntary physical activity affects body composition, bone mass indices and cortical bone gene expression in a modality dependent manner. Voluntary physical activity has the ability to modulate the body composition and gene expression changes induced by a high-fat diet. In the bone marrow, the transcriptome retains a memory of the early life physical activity 60 days after exercise has ceased. The potential mechanisms driving the gene expression response must be the focus of future studies.