Neuroregulation of nonexercise activity thermogenesis and obesity resistance

Abstract

High levels of spontaneous physical activity in lean people and the nonexercise activity thermogenesis (NEAT) derived from that activity appear to protect lean people from obesity during caloric challenge, while obesity in humans is characterized by dramatically reduced spontaneous physical activity. We have similarly demonstrated that obesity-resistant rats have significantly greater spontaneous physical activity than obesity-prone rats, and that spontaneous physical activity predicts body weight gain. Although the energetic cost of activity varies between types of activity and may be regulated, individual level of spontaneous physical activity is important in determining propensity for obesity. We review the current status of knowledge about the brain mechanisms involved in controlling the level of spontaneous physical activity and the NEAT so generated. Focus is on potential neural mediators of spontaneous physical activity and NEAT, including orexin A (also known as hypocretin 1), agouti-related protein, ghrelin, and neuromedin U, in addition to brief mention of neuropeptide Y, corticotrophin releasing hormone, cholecystokinin, estrogen, leptin, and dopamine effects on spontaneous physical activity. We further review evidence that strain differences in orexin stimulation pathways for spontaneous physical activity and NEAT appear to track with the body weight phenotype, thus providing a potential mechanistic explanation for reduced activity and weight gain.

The biological control of voluntary exercise, spontaneous physical activity and daily energy expenditure in relation to obesity: human and rodent perspectives

“…Vaanholt et al, 2008;Gebczynski and Konarzewski, 2009a;Gebczynski and Konarzewski, 2009b). Here, as elsewhere, one needs to be extremely careful when reading the literature to note what a particular study actually means by 'locomotor activity', as it is often used to describe either activity in home cages after a period of acclimation or habituation (of main interest in the present review) (see also Kotz et al, 2008), locomotion in acute tests in novel arenas (e.g. open-field tests) (see also Viggiano, 2008;Hesse et al, 2010) or even wheel running.…”

“…fidgeting, non-specific ambulatory behaviour (pacing)], and this is often termed SPA (e.g. Ravussin et al, 1986;Kotz et al, 2008). Again, such activity can vary greatly in both intensity and duration.…”

Developmental programming of energy balance regulation: is physical activity more ‘programmable’ than food intake?

“…This insight is particularly timely, in that modernisation is leading to a worldwide epidemic of physical inactivity (29) . Physical activity clearly has a genetic component (30,31) and plays an important role in protecting some individuals from obesity (32)(33)(34) . Based on a scholarly review of the literature on the biological basis of physical activity, Rowland proposed that each individual is endowed with a specific set point (the activity-stat) that determines his or her propensity for physical activity (35) .…”

“…Voluntary exercise is physical activity that is not directly needed for survival or influenced by any outside factors, whereas SPA is all physical activity that is not voluntary exercise, including activities of daily-living and pacing and fidgeting (32) . In rodents, running wheel activity is the universal model for voluntary exercise (32) , and home cage activity is indicative of SPA (34) . In what we believe was the first reported animal data suggesting developmental programming of physical activity, Vickers et al (36) studied a rat model of maternal undernutrition (30 % of ad libitum intake) throughout pregnancy, and examined effects on the offspring.…”

Functional Genomic Architecture of Predisposition to Voluntary Exercise in Mice: Expression QTL in the Brain

“…In addition, selective breeding for both elevated endurance capacity in rats and elevated wheel running in mice has resulted in alterations to neurobiological pathways that appear to delay the onset of exercise-induced fatigue (rats: Foley et al 2006) and increase motivation for wheel-running behavior (mice: Rhodes et al 2005). Although a detailed understanding of the neurobiology of exercise is still years away, potential mechanistic foundations include multiple brain regions encompassing interactions between neurotransmitters, peptides, and hormones (see figure 1 in Kotz et al 2008; figure 5 in Garland et al 2011b). More specifically, pharmacological experiments on mice selectively bred for elevated wheel running have implicated alterations in dopamine function (Rhodes et al 2005;Knab and Lightfoot 2010;Mathes et al 2010) and endocannabinoid signaling (Keeney et al 2008) as underlying the neurobiology of high voluntary exercise.…”