Thermoneutral Housing Enables Studies of Vertical Transmission of Obesogenic Diet-Driven Metabolic Diseases

Abstract

Vertical transmission of obesity is a critical contributor to the unabated obesity pandemic and the associated surge in metabolic diseases. Existing experimental models insufficiently recapitulate “human-like” obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL/6 background, we present a tractable, more “human-like” approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.

Housing temperature dictates the systemic and tissue-specific molecular responses to cancer in mice

“…Unlike humans, whose thermoneutral zone lies at ambient temperature, housing laboratory mice at ambient or standard temperature (ST; 20-22°C) results in metabolic adaptations driven by cold stress-induced thermogenic activity, which do not occur when housing mice at their thermoneutral zone (TN; 28-32°C 4 ). In fact, we and others have shown that, compared to TN housing, ST housing affects metabolic adaptations in preclinical models of obesity 5 , insulin action 6 , and in response to exercise 7,8 , showing that housing mice under cold stress represents a substantial confounding factor. Albeit CC is considered a metabolic condition, the impact of housing temperature on murine CC remains unexplored.…”

“…All mice were shaved the right flank one day prior to the inoculation. All mice were subcutaneously injected with PBS with or without 5 x 10 5 C26 cells into the flank. Body weight and composition, as well as food intake, were monitored once a week during the first fourteen days after C26 cell inoculation, and twice a week after that.…”