Individual housing of male C57BL/6J mice after weaning impairs growth and predisposes for obesity

Abstract

For (metabolic) research models using mice, singly housing is widely used for practical purposes to study e.g. energy balance regulation and derangements herein. Mouse (social) housing practices could however influence study results by modulating (metabolic) health outcomes. To study the effects of the social housing condition, we assessed parameters for energy balance regulation and proneness to (diet induced) obesity in male C57Bl/6J mice that were housed individually or socially (in pairs) directly after weaning, both at standard ambient temperature of 21˚C. During adolescence, individually housed mice had reduced growth rate, while energy intake and energy expenditure were increased compared to socially housed counterparts. At 6 weeks of age, these mice had reduced lean body mass, but significantly higher white adipose tissue mass compared to socially housed mice, and higher UCP-1 mRNA expression in brown adipose tissue. During adulthood, body weight gain of individually housed animals exceeded that of socially housed mice, with elevations in both energy intake and expenditure. At 18 weeks of age, individually housed mice showed higher adiposity and higher mRNA expression of UCP-1 in inguinal white but not in brown adipose tissue. Exposure to an obesogenic diet starting at 6 weeks of age further amplified body weight gain and adipose tissue deposition and caused strong suppression of inguinal white adipose tissue mRNA UCP-1 expression. This study shows that post-weaning individual housing of male mice impairs adolescent growth and results in higher susceptibility to obesity in adulthood with putative roles for thermoregulation and/or affectiveness.

Neurobiological Mechanisms Modulating Emotionality, Cognition and Reward-Related Behaviour in High-Fat Diet-Fed Rodents

“…Interestingly, some neuroadaptations produced by HFD treatment parallel those observed with cocaine (see summary in Supplementary Table S2). For example, cocaine exposure produced slight changes in glucose and phospholipid metabolism as well as neurotransmission and increased oxidative stress in the NAc [165,166]. In addition, similar to observations made with HFD treatment [144], cocaine exposure increased oxidative stress and reduced mitochondrial activity in isolated synaptosomes from the whole brain [167].…”

“…Importantly, both the schedule of HFD consumption and the social housing conditions (single- versus group-housed animals) seem to modulate the outcomes of psychostimulant-related behaviours. A recent study suggested that the post-weaning housing condition could modulate the susceptibility to HFD-induced body weight gain, adiposity and thermoregulation in male mice [ 165 ], highlighting the need to consider the housing density in the interpretation of the behavioural and metabolic data.…”

“…Because the mitochondrial DNA (mtDNA) copy number was reported to be increased in the prefrontal cortex and hippocampus of rats with a history of cocaine self-administration [169], perhaps the variation in mtDNA compensated a decreased number of mitochondria or mitochondrial synthesis in order to maintain a normal level of mitochondrial transcription to provide ATP [170]. A history of cocaine self-administration induced neuroplasticity in the NAc through alterations in the pattern of genes important in several mitochondrial functions (e.g., mitochondrial transcription and replication, mitochondrial dynamics and energy production) [165,171,172]. The possible mechanisms underlying the changes in molecular correlates of mitochondrial dysfunction by cocaine have yet to be determined, but they may occur in response to the massive DA release due to cocaine binding to transporter sites of monoamines, as well as from the oxidative potential of cocaine metabolites [49].…”

“…Importantly, cocaine oppositely modulated the accumbal mitochondrial morphology and the mRNA expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc1α), a master regulator of mitochondrial biogenesis, and dynamin-1 like (Drp1), a regulator of mitochondrial division, in dopamine receptor D1-expressing medium spiny neurons (D1-MSNs) and dopamine receptor D2-expressing MSNs (D2-MSNs) [165,171,172]. Because cocaine has been reported to produce contrasting effects on dendritic spine density, excitatory plasticity, signalling processes and transcriptional activity in D1-MSNs and D2-MSNs [173,174], further work is needed to understand the importance of mitochondria in cocaine behavioural plasticity in specific neuronal subtypes.…”

Common Dietary Modifications in Preclinical Models to Study Skeletal Health

“…While controls should also be individually housed, this does introduce metabolic and behavioral disruption to the animals. Individual housing of mice has been shown to reduce growth rate while increasing energy intake and expenditure, due in part to maintain thermal neutrality without huddling of litter ( 50 ). Behavioral and endocrine alterations are also noted during individual housing and vary in degree amongst different mouse strains (e.g., BALB/c demonstrate increased anxiety-like behavior versus Swiss Webster which are considered ‘normal’); however, they should be considered when using this model ( 51 ).…”