Background Increasing physical activity reduces obesity complications. In female mice with dietary or metabolic obesity, exercise maintains insulin sensitivity, reduces adipose inflammation, and improves liver histology1. Male gender is associated with a worse metabolic phenotype in mice. We therefore tested whether exercise can delay onset of obesity, and ameliorate metabolic phenotype in male mice by improving adipose morphology and function.
Methods Male Alms1-/- (foz/foz) NOD.B10 mice and Wt littermates (8/group), fed atherogenic (high fat/sugar/cholesterol) diet, were caged in pairs until 24 week-old. Half the cages were fitted with an exercise wheel and cycle computer. Blood, liver, and lumbar/epididymal/mesenteric white adipose tissue were removed.
Results Wt mice ran ~8km/day, whereas foz/foz mice ran ~1.5km/day; foz/foz mice were notably less active and showed a decrease in wheel use towards the end of study. Exercise delayed but failed to prevent development of severe obesity in foz/foz mice; all foz/foz mice weighed ~57g at Week 24. Exercising Wt mice weighed less than non-exercising counterparts (~34g vs. ~44g; P<0.05). There were also reductions in liver and adipose depot weights in exercising Wt mice (P<0.05), but not in foz/foz mice. Exercise improved hyperglycemia and insulin sensitivity in Wt but not foz/foz mice. Exercise improved morphometry and reduced inflammatory recruitment in all adipose compartments in Wt mice, but failed to improve adipose dysfunction in foz/foz mice. Hepatic lipid partitioning was less in exercising Wt but not foz/foz mice vs. non-exercising; exercise normalized liver histology and abolished fibrosis in Wt mice.
Conclusions Exercise confers metabo-protective effects in mice with dietary obesity (atherogenic diet-fed Wt) by reducing adipose inflammation and improving adipose morphometry, and this corrects fatty livers. Diabetic mice with metabolic obesity (atherogenic diet-fed foz/foz) were reluctant to use the wheel, perhaps secondary to excessive weight gain, and resultant mild exercise failed to confer benefits on the metabolic phenotype.