Caloric restriction prevents the development of airway hyperresponsiveness in mice on a high fat diet

Abstract

We have previously shown that high fat diet (HFD) for 2 weeks increases airway hyperresponsiveness (AHR) to methacholine challenge in C57BL/6J mice in association with an increase in IL-1β levels in lung tissue. We hypothesize that obesity increases AHR via the IL-1β mechanism, which can be prevented by caloric restriction and IL-1β blockade. In this study, we fed C57BL/6J mice for 8 weeks with several hypercaloric diets, including HFD, HFD supplemented with fructose, high trans-fat diet (HTFD) supplemented with fructose, either ad libitum or restricting their food intake to match body weight to the mice on a chow diet (CD). We also assessed the effect of the IL-1β receptor blocker anakinra. All mice showed the same total respiratory resistance at baseline. All obese mice showed higher AHR at 30 mg/ml of methacholine compared to CD and food restricted groups, regardless of the diet. Obese mice showed significant increases in lung IL-1 β mRNA expression, but not the protein, compared to CD and food restricted mice. Anakinra abolished an increase in AHR. We conclude that obesity leads to the airway hyperresponsiveness preventable by caloric restriction and IL-1β blockade.

Caloric restriction attenuates C57BL/6J mouse lung injury and systemic toxicity induced by real ambient particulate matter exposure

“…Healthy individuals undergoing short-term CR have been shown to have reduced monocyte metabolic and inflammatory activity and a drastic decrease in circulating and organ monocyte numbers [55,56]. The recruitment of inflammatory cells in tissues and airway induced by intake of high fat or high caloric diet could be reversed by CR [57,58]. In this study, our results established that CR could reduce the levels of pulmonary and circulating inflammatory triggers.…”

“…Dietary intake could interact with xenobiotic response elements (XREs) to regulate the expression and activity of metabolizing enzymes, thus modifying the cellular response to xenobiotic stressors [60,61]. A line of evidence has demonstrated that CR acts as a modulator of XREs and up-regulation of the expression of enzymes involved in phase I, phase II metabolism and xenobiotic transport in mouse liver [29,58,62]. CR led to an increase in microsomal enzyme activity of cytochrome P450 (CYP450), modifying phase I metabolism of environmental toxicants [30,31].…”

IL-33, diet-induced obesity, and pulmonary responses to ozone

“…Similarly, IL-33 is proposed to protect against the adipose tissue inflammation of obesity [40,41]. Increases in IL-1β and TNFα, have been proposed to contribute to the innate AHR of obesity [42][43][44]. Hence, we considered the possibility that ST2 deficiency augmented innate AHR in HFD-fed mice (Fig.…”

Caloric restriction attenuates C57BL/6J mouse lung injury and extra-pulmonary toxicity induced by real ambient particulate matter exposure

“…Healthy individuals undergoing short-term CR have been shown to have reduced monocyte metabolic and in ammatory activity and a drastic decrease in circulating and organ monocyte numbers [59,60]. The recruitment of in ammatory cells in tissues and airway induced by intake of high fat or high caloric diet could be reversed by CR [61,62]. In this study, we establish that CR could reduce the levels of pulmonary and circulating in ammatory triggers.…”

“…Dietary intake could interact with xenobiotic response elements (XREs) to regulate the expression and activity of metabolizing enzymes, thus modifying the cellular response to xenobiotic stressors [64,65]. A line of evidence has demonstrated that CR acts as a modulator of XREs and up-regulation of the expression of enzymes involved in phase I, phase II metabolism and xenobiotic transport in mouse liver [30,62,66]. CR led to an increase in microsomal enzyme activity of cytochrome P450 (CYP450), modifying phase I metabolism of environmental toxicants [31,32].…”