Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Abstract

Background A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short‐term high‐fat diet (HFD) feeding on the development of allergic asthma. Objective To delineate the impact of short‐term HFD feeding on the development of experimental allergic asthma. Methods Female C57BL/6JRJ mice were fed with a short‐term HFD or chow diet (CD) for 12 weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)‐mediated activation of T cells. Results Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD‐fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD‐fed mice. Mucus production was similar in both treatment groups. OVA‐induced increases in DC and CD4+ T‐cell recruitment to the lungs were significantly attenuated in HFD‐fed mice. MHC‐II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD‐fed compared to CD‐fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation. Conclusions/clinical relevance These findings suggest that short‐term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC‐II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short‐term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.

Sex differences in the influence of obesity on a murine model of allergic lung inflammation

“…The authors suggested that this is an effect related to the short‐term of the diet and not to the obesogenic phenotype per se. The authors reported that HFD female mice presented a reduced airway hyperresponsiveness, airway inflammation, diminished Th1/TH17 but unchanged TH2 differentiation . These results are in line with our observations, where females also presented an attenuated inflammatory response to OVA after an even shorter high‐fat diet of 8 weeks.…”

Impact of diet and the bacterial microbiome on the mucous barrier and immune disorders

“…A similar experiment in female mice showed that HFD reduced inflammation and AHR due to an impaired ability of pulmonary DCs to induce T h 1 and T h 17 responses 90 . Although lung mucus production was comparable to levels in control diet‐fed mice, there was no investigation of GI tissues and it is unclear whether an HFD‐induced increase in faecal Proteobacteria and decrease in Firmicutes may have impacted the GI mucous barrier 90 . Sex‐specific differences in HFD‐induced obesity and AAD are well documented, 211 and further research may elucidate the effect of microbiota on these differences.…”

“…There is less evidence of interactions between dietary lipids, the microbiome and lung mucus barrier in healthy states. Although mice fed HFDs have altered GI microbiome composition and develop respiratory inflammation, histopathology and impaired lung function, they do not have altered lung mucus production without another stimulus such as in disease models 57,90,133 . More detailed analysis of mucus composition and characterization of the respiratory microbiome would provide further insights.…”

Developments allergy in 2019 through the eyes of clinical and experimental allergy, part I mechanisms

“…Schroder and colleagues examined the effect of short-term HFD, mild weight gain on the induction of the asthma phenotype in mice. 35 In these studies, the author show that female (C57BL6JRJ) mice feed HFD to induce mild increase in body weight accompa- The two studies clearly show that metainflammation can alter allergic disease susceptibility and severity and that further in-depth studies will be required to fully decipher the mechanism of action.…”

“…Schroder and colleagues examined the effect of short‐term HFD, mild weight gain on the induction of the asthma phenotype in mice 35 . In these studies, the author show that female (C57BL6JRJ) mice feed HFD to induce mild increase in body weight accompanied by mild metabolic alterations develop a less severe asthma phenotype.…”