Metabolic risk factors in mice divergently selected for BMR fed high fat and high carb diets

Abstract

Factors affecting contribution of spontaneous physical activity (SPA; activity associated with everyday tasks) to energy balance of humans are not well understood, as it is not clear whether low activity is related to dietary habits, precedes obesity or is a result of thereof. In particular, human studies on SPA and basal metabolic rates (BMR, accounting for >50% of human energy budget) and their associations with diet composition, metabolic thrift and obesity are equivocal. To clarify these ambiguities we used a unique animal model—mice selected for divergent BMR rates (the H-BMR and L-BMR line type) presenting a 50% between-line type difference in the primary selected trait. Males of each line type were divided into three groups and fed either a high fat, high carb or a control diet. They then spent 4 months in individual cages under conditions emulating human “sedentary lifestyle”, with SPA followed every month and measurements of metabolic risk indicators (body fat mass %, blood lipid profile, fasting blood glucose levels and oxidative damage in the livers, kidneys and hearts) taken at the end of study. Mice with genetically determined high BMR assimilated more energy and had higher SPA irrespective of type of diet. H-BMR individuals were characterized by lower dry body fat mass %, better lipid profile and lower fasting blood glucose levels, but higher oxidative damage in the livers and hearts. Genetically determined high BMR may be a protective factor against diet-induced obesity and most of the metabolic syndrome indicators. Elevated spontaneous activity is correlated with high BMR, and constitutes an important factor affecting individual capability to sustain energy balance even under energy dense diets.

Functional and structural changes in aorta of mice divergently selected for basal metabolic rate

“…Irrespective of age, high RMR/BMR constitutes an independent mortality risk in humans (Sadowska et al 2017;Schrack et al 2014). Therefore, the thickening of myointimal layer, observed in the HBMR mice, constitute an unique model to test for a risk of cellular drain, vascular disturbances, and CV-related morbidity in individuals with a higher rate of energy turnover.…”

“…According to previous studies, BMR is strongly correlated with the mass of internal organs such as heart, liver, kidney and small intestine (Brzęk et al 2007;Konarzewski and Książek 2013), and-for example-with a size of cells building those organs (Maciak et al 2014). Therefore, increasing evidence from both, studies on humans and animal models suggest that physiological and anatomical differences in the rate of metabolism can translate into susceptibility to the development of serious illnesses (Ghebre et al 2016;Kathiresan and Srivastava 2012;Maciak and Michalak 2015;Nunney 2018;Sadowska et al 2017).…”

“…Similarly, the pro-inflammatory status of an organism and overall immunological activation are correlated with an increased BMR, which remains attributable to overall metabolic dysregulations and considered the main indicator of mortality (Ferrucci et al 2005;Heilbronn et al 2006). Conversely, below-average BMR is associated with metabolic thrift and obesity (Hamilton et al 2007;Sadowska et al 2017). Moreover, variation in the rate of metabolism translates not only to physiological, but also to anatomical differentiation.…”

“…This must be based on the recognition of the complex multifactorial traits directly related to CVD rather than simplified molecular genetics (Russell and Proctor 2006). To fill this gap, here we used laboratory mice from longterm divergent selection for high and low basal metabolic rate, characterized by a 50% differentiation in BMR that is unmatched by any other animal model (Sadowska et al 2017). Apart from the difference in BMR, the lines differ distinctly with respect to the relative sizes of metabolically active internal organs, including heart (Konarzewski and Książek 2013) as well as metabolic risk indicators, such as per cent of body fat mass, blood lipid profile and fasting blood glucose levels (Sadowska et al 2017).…”

Spontaneous Physical Activity Defends Against Obesity

“…Recent evidence has explored whether other traits related to energy balance and physical activity are correlated with or influence SPA. For example, aerobic capacity does not correlate with SPA [56] while basal metabolic rate does [57], and the evidence is still mixed as to the effects of voluntary exercise on SPA [58–61]. Future challenges include the accurate measurement of SPA, its different components and NEAT, the possibility of measuring SPA and NEAT in group housed animals, and accurate comparison of the physiological effects and mechanisms of SPA between males and females.…”