Aldosterone deficiency in mice burdens respiration and accentuates diet-induced hyperinsulinemia and obesity
Wan-Hui Liao, … , Maciej Henneberg, Wolfgang Langhans
Wan-Hui Liao, … , Maciej Henneberg, Wolfgang Langhans
Published July 26, 2018
Citation Information: JCI Insight. 2018;3(14):e99015. https://doi.org/10.1172/jci.insight.99015.
View: Text | PDF
Research Article Endocrinology Metabolism

Aldosterone deficiency in mice burdens respiration and accentuates diet-induced hyperinsulinemia and obesity

Abstract

Aldosterone synthase inhibitors (ASIs) should alleviate obesity-related cardiovascular and renal problems resulting partly from aldosterone excess, but their clinical use may have limitations. To improve knowledge for the use of ASIs, we investigated physiology in aldosterone synthase–knockout (ASKO) mice. On regular chow diet (CD), ASKO mice ate more and weighed less than WT mice, largely because they hyperventilated to eliminate acid as CO2. Replacing CD with high-fat diet (HFD) lessened the respiratory burden in ASKO mice, as did 12- to 15-hour fasting. The latter eliminated the genotype differences in respiratory workload and energy expenditure (EE). Thus, aldosterone deficiency burdened the organism more when the animals ate carbohydrate-rich chow than when they ate a HFD. Chronic HFD exposure further promoted hyperinsulinemia in ASKO mice that contributed to visceral fat accumulation accompanied by reduced lipolysis, thermogenic reprogramming, and the absence of weight-gain-related EE increases. Intracerebroventricular aldosterone supplementation in ASKO mice attenuated the HFD-induced hyperinsulinemia, but did not affect EE, suggesting that the presence of aldosterone increased the body’s energetic efficiency, thus counteracting the EE-increasing effect of low insulin. ASIs may therefore cause acid-overload-induced respiratory burden and promote obesity. Their use in patients with preexisting renal and cardiopulmonary diseases might be contraindicated.

Authors

Wan-Hui Liao, Claudia Suendermann, Andrea Eva Steuer, Gustavo Pacheco Lopez, Alex Odermatt, Nourdine Faresse, Maciej Henneberg, Wolfgang Langhans

×

Figure 5

Switching from chow diet (CD) to high-fat diet (HFD) feeding reduced the respiratory burden in ASKO mice.

Options: View larger image (or click on image) Download as PowerPoint
Switching from chow diet (CD) to high-fat diet (HFD) feeding reduced the...
Unlike in WT mice, chronic HFD feeding did not increase energy expenditure (EE) in ASKO mice. (A–C) AUC of (A) EE (B) O2 consumption (C) CO2 production of CD-fed (5 weeks) and HFD-fed (5 and 10 weeks) WT and ASKO mice (n = 5–7/group, mean ± SEM). *P < 0.05, CD-fed ASKO versus CD-fed WT or 5-week HFD-fed ASKO versus 5-week HFD-fed WT. #P < 0.05, 10-week HFD-fed WT versus CD-fed WT. ##P < 0.01, 10-week HFD-fed WT versus 5 week HFD-fed WT. †P < 0.05, CD-fed ASKO versus 5-week HFD-fed ASKO. (D) Daily energy intake (n = 6–12/group, mean ± SEM). **P < 0.01 CD-fed ASKO versus CD-fed WT or 5-week HFD-fed ASKO versus 5-week HFD-fed WT. (E) Changes in EE in response to refeeding of CD or HFD for 3.5 hours in 15-hour fasted, 3-month-old mice. Changes in EE = AUC EE following diet for 3.5 hours – AUC EE before diet for 3.5 hours. Fasting-refeeding was performed in the same mice, first with CD and 4 days later with HFD (n = 5–7/group, mean ± SEM). All data analyzed by Welch’s unpaired t test. In A–C, data of CD-fed (5 weeks) mice are also shown in Figure 2A and Supplemental Figure 4, A and B.