Obesity amplifies influenza virus-driven disease severity in male and female mice

Alarcon, Pablo C.; Damen, Michelle S.M.A.; Ulanowicz, Cassidy J.; Sawada, Keisuke; Oates, Jarren R.; Toth, Andrea; Wayland, Jennifer L.; Chung, Hak; Stankiewicz, Traci E.; Moreno-Fernandez, Maria E.; Szabo, Sara; Zacharias, William J.; Divanovic, Senad

doi:10.1016/j.mucimm.2023.09.004

Cited by 3 publications

(2 citation statements)

References 62 publications

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“…We also noted a more severe offspring phenotype with use of our severely obese maternal model, including increased offspring mortality during or shortly after birth and in the first few days of life. This phenotype has been scarcely described in mouse models of DIO [112] but closely mimics the human phenotype of increased risk of stillbirth in mothers with obesity-something that adds to the growing list of examples where TN housing allows for a closer recapitulation of human physiology and disease (e.g., cancer [72,73], atherosclerosis [21,74], asthma [75], liver disease [77], and influenza [78]). In fact, increased offspring mortality in severely obese mothers is likely related to insufficient intrauterine nutrition [58,113], while increased mortality within the first few days of life is likely due to impaired lactation or mothering behavior [114,115].…”

Section: Discussionmentioning

confidence: 95%

“…Such modulation of mouse physiology has allowed TN housing to improve mimicry of many human disease models, including cancer [64,[70][71][72][73], atherosclerosis [21,74], asthma [75], food allergy [76], and liver disease [77]. Specifically, TN housing allows for induction of HFD-induced severe obesity and amplifies severity of obesity-associated sequelae (e.g., glucose dysmetabolism, hepatocellular damage, influenza virus infection pathology) in WT female C57BL/6 mice [20,78]. However, whether the coupling of TN housing with HFD enables studies of vertical transmission of obesity is not known.…”

Section: Introductionmentioning

confidence: 99%

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

Wayland,

Doll,

Lawson

et al. 2023

Nutrients

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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.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

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

Wayland,

Doll,

Lawson

et al. 2023

Nutrients

Self Cite

View full text Add to dashboard Cite

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Upregulation of inflammatory genes and pathways links obesity to severe COVID-19

Currey,

Ellsworth,

Khatun

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Obesity-Associated Changes in Immune Cell Dynamics During Alphavirus Infection Revealed by Single Cell Transcriptomic Analysis

Hameed,

Daamen,

Hossain

et al. 2024

Preprint

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Obesity induces diverse changes in host immunity, resulting in worse disease outcomes following infection with various pathogens, including arthritogenic alphaviruses. However, the impact of obesity on the functional landscape of immune cells during arthritogenic alphavirus infection remains unexplored. Here, we used single-cell RNA sequencing (scRNA-seq) to dissect the blood and tissue immune responses to Mayaro virus (MAYV) infection in lean and obese mice. Footpad injection of MAYV caused significant shifts in immune cell populations and induced robust expression of interferon response and proinflammatory cytokine genes and related pathways in both blood and tissue. In MAYV-infected lean mice, analysis of the local tissue response revealed a unique macrophage subset with high expression of IFN response genes that was not found in obese mice. This was associated with less severe inflammation in lean mice. These results provide evidence for a unique macrophage population that may contribute to the superior capacity of lean mice to control arthritogenic alphavirus infection.

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Obesity amplifies influenza virus-driven disease severity in male and female mice

Cited by 3 publications

References 62 publications

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

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

Upregulation of inflammatory genes and pathways links obesity to severe COVID-19

Obesity-Associated Changes in Immune Cell Dynamics During Alphavirus Infection Revealed by Single Cell Transcriptomic Analysis

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