Musculoskeletal health in response to the combined effect of age and an obesogenic diet in male C57BL/6J mice
Authors: Bott Kirsten N , Gittings William , Fajardo Val Andrew , Vandenboom Rene , LeBlanc Paul J , Ward Wendy E , Peters Sandra J 
Published: November 2023

Aging and obesity are two major aspects that can negatively impact musculoskeletal structure and function; however, their combined effects have not been well investigated. Thus, the study objective was to investigate the combined effects of aging and diet‐induced obesity, via high‐fat sucrose (HFS) diet, on bone and muscle structure and function in mice. Bone to muscle ratios were calculated since these tissues are inter‐dependent with an established mechanical relationship.Male C57BL/6J mice were randomized to control (AGE, AIN93M, 10.3% kcal fat, 100 g/kg sucrose) or HFS (HFS‐AGE, 45.3% kcal fat 200 g/kg sucrose) diet for 13 weeks from 20 weeks of age. Proximal tibia trabecular bone structure, volumetric bone mineral density (vBMD), and body composition were measured longitudinally at 20, 24, 28, and 32 weeks of age. In vitro contractile measures were performed on isolated soleus and extensor digitorum longus (EDL) muscles at baseline (BSL, 21 weeks of age, n=11) and at the end of the 13‐week intervention when AGE (n=12) and HFS‐AGE (n=12) mice were 33 weeks of age.Following the 13‐week intervention, HFS‐AGE weighed +30% more than AGE (p<0.0001), had a greater decrease in lean mass (AGE −13%; HFS‐AGE −46%, p<0.0001), greater increase in fat mass (AGE +51%, HFS‐AGE +79%, p<0.0001), and an increase in bone mass for AGE (+15%), but a decrease for HFS‐AGE (−27%, p<0.0001).Both AGE and HFS‐AGE had similar declines in trabecular bone with age: percent bone volume (BV/TV, AGE −34%, p<0.0001; HFS‐AGE −45%, p<0.0001), trabecular thickness (Tb.Th, AGE −9%, p<0.05; HFS‐AGE −8%, p<0.05), trabecular number (Tb.N, AGE −29%, p<0.05; HFS‐AGE −41%, p<0.05), vBMD (AGE −17%, p<0.001; HFS‐AGE −23%, p<0.001). There was also an increase in trabecular separation (Tb.Sp) for HFS‐AGE only (+19%, p<0.05) with age. For muscle contractile function, HFS‐AGE resulted in larger soleus cross‐sectional area (CSA) compared AGE (p>0.001), but this did not translate to greater twitch or tetanus peak force.The ratio of outcomes of bone to muscle declined in both groups due to a greater decline in key measures of bone structure (BV/TV) than muscle function (soleus and EDL peak tetanus and CSA) and was not altered by HFS. For the soleus, there were decreases in the following ratios compared to BSL: BV/TV to soleus peak tetanus (AGE −48%, p<0.01), BV/TV to soleus CSA (AGE −36%, p<0.01; HFS‐AGE −48%, p<0.001), vBMD to soleus peak tetanus (AGE −23%, p<0.05), and vBMD to soleus CSA (HFS‐AGE −30%, p<0.001). In addition, the vBMD to peak tetanus was lower for AGE compared to HFS‐AGE (−23%, p<0.05) and vBMD to soleus CSA was lower for the HFS‐AGE compared to AGE (−21%, p<0.05). While for the EDL, the following ratios decreased compared to BSL: BV/TV to EDL peak tetanus (AGE −41%, p<0.05), BV/TV to EDL CSA (AGE −46%, p<0.0001; HFS‐AGE −61%, p<0.01), and vBMD to EDL CSA (AGE −23%, p<0.01; HFS‐AGE −24%, p<0.01).In conclusion, consumption of a HFS diet during middle age did not exacerbate age‐related declines in bone or alter muscle function, but these tissues do not decline in a coordinate manner. During aging, bone structure declined at a greater rate than muscle function.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada, Canadian Foundation for Innovation, K.N.B. is funded through an Ontario Graduate Scholarship