Obesity, rather than high fat diet, exacerbates the outcome of influenza virus infection in influenza-sensitized mice

Authors: GUO, WEIMAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; LI, LIJUN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; DING, SAMUEL - Tufts University; MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Frontiers in Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/7/2022
Publication Date: 10/20/2022
Citation: Guo, W., Wu, D., Li, L., Ding, S., Meydani, S.N. 2022. Obesity, rather than high fat diet, exacerbates the outcome of influenza virus infection in influenza-sensitized mice. Frontiers in Nutrition. https://doi.org/10.3389/fnut.2022.1018831.
DOI: https://doi.org/10.3389/fnut.2022.1018831

Interpretive Summary: Studies have shown that obesity is associated with impaired immune function and increased risk of infections. High-fat diet-induced obesity is a commonly used animal model for obesity research. However, due to the fact that high-fat diet itself can affect immune function, it is not clear if the immune impairment is caused by obesity per se or directly by the high fat content in the diet. Using CD-1 mice, an outbred mice strain that had highly heterogeneous weight gain in response to high fat feeding, we investigated this issue. CD-1 mice that were fed high-fat or low-fat diets received influenza vaccine before they were infected with influenza virus. We found that CD-1 mice that became obese after high fat feeding exhibited more severe symptom of influenza infection compared to those that had normal weight. Our results suggest that obesity, rather than high-fat diet itself, may be responsible for the impaired immunity.

Technical Abstract: Introduction: Obesity is associated with impaired immune function and increased susceptibility to infection. High fat (HF) diet-induced obesity is a commonly used animal model. However, HF diet itself is known to affect immune function and infection. Thus, it is not discernable which one, HF diet or adiposity, is the major contributor to the observed impairment in immunity and susceptibility to infection in HF diet-induced obesity. We hypothesized that obesity is a major contributor to impaired immune function. Method and Results: Weight-matched outbred female CD-1 mice (1-mo) were randomly assigned to either a HF (45%) or a low fat (LF, 10%) diet group. Ten wk after feeding their respective diets, weight gain in the mice fed the HF diet varied greatly. Thus, based on the average body weight, mice in HF diet group were divided into two sub-groups: HF lean (HF-L) and HF obese (HF-O). After 25-wk, mice were immunized with an influenza A/Puerto Rico/8/34 vaccine and boosted 3-wk later. Five wk after the booster, mice were infected with influenza A/Puerto Rico/8/34 virus, and body weight was recorded daily for one month. HF-O mice exhibited significant weight loss after influenza virus challenge compared to LF and HF-L mice while LF and HF-L mice largely maintained their weight to a similar extent. Conclusion: Our findings suggest that obesity, rather than HF diet, per se, may impair the efficacy of influenza vaccination.