Cardiac specific deletion of KLF15 alters tissue and plasma levels of free fatty acids and triglycerides.

<p>Cardiac FFA (A) and TG (B) levels in control (MHC-Cre) vs. KF15-cKO following 48 hours fasting, (n = 5), *P<0.05 vs. Cre Fed, **P<0.05 vs. CKO Fed, # P<0.05 vs. Cre Fast. Plasma FFA (C) and TG (D) levels in control (MHC-Cre) vs. KLF15-cKO following 48 hours fasting, (n = 5), *P<0.05 vs. Cre Fed, **P<0.05 vs. CKO Fed, # P<0.05 vs. Cre Fast.</p

Short-chain diet rescues the KLF15-dependent attenuation of cardiac function in response to fasting.

<p>(A) qPCR analysis of expression of transporter genes in MHC-Cre vs. KLF15-cKO under fed vs. 48 hour fasting conditions. *P<0.05 vs. Cre Fed, **P<0.05 vs. CKO Fed, # P<0.05 vs. Cre Fast. Values normalized to <i>Ppib</i>. (B) <i>Slc25a20</i> expression (qPCR) in MHC-Cre vs. KLF15-cKO under fed vs. 48 hour fasting conditions. *P<0.05 vs. Cre Fed, **P<0.05 vs. CKO Fed, # P<0.05 vs. Cre Fast. Values normalized to <i>Ppib</i>. (C) Western blot analysis of CACT levels in MHC-Cre vs KLF15-cKO under fed and 48 hour fasting conditions. α-tubulin used as loading control. (D) Quantification of data in C (n = 3 per group). Two-tailed Student's <i>t</i>-test for unpaired data was used. *P<0.05. (E) Left ventricular fractional shortening from echocardiography performed in control (MHC-Cre) vs. KLF15-cKO under fed vs. 48 hours fasting conditions following 10 weeks of short-chain fatty acid diet, (n = 10). (F) Representative echocardiography image from MHC-Cre vs. KLF15-cKO following 48 hours fasting and 10 weeks of short-chain fatty acid diet. (G) Tabular representation of echocardiography data in MHC-Cre vs. KLF15-cKO under fed vs. 48 hour fasting conditions following 10 weeks of short-chain fatty acid diet.</p

Cardiac KLF15 is required for the heart’s functional adaptation in response to fasting.

<p>(A) Left ventricular fractional shortening from echocardiography performed in control (MHC-Cre) vs KLF15-cKO under fed vs. 48 hours fasting conditions, (n = 5), *P<0.05 vs. MHC-Cre Fast. (B) Representative echocardiography image from MHC-Cre vs. KLF15-cKO following a 48 hour fast. (C) Tabular representation of echocardiography data in MHC-Cre vs. KLF15-cKO under fed vs. 48 hour fasting conditions.</p

Cardiac specific deletion of KLF15 alters lipid profile.

<p>Metabolomic analysis of long chain acylcarnitines in cardiac tissue from control (MHC-Cre) vs. KLF15-cKO with and without 48 hour fast, (n = 5), *P<0.05 by one-way analysis of variance (ANOVA) with the Tukey post hoc test.</p

Change in long chain acylcarnitine profiles after loss of cardiac KLF15 expression.

<p>Change in long chain acylcarnitine profiles after loss of cardiac KLF15 expression.</p

Systemic KLF15 is required for the heart’s functional adaptation in response to fasting.

<p>(A) Left ventricular fractional shortening from echocardiography performed in wild-type (WT) vs. systemic <i>Klf15</i>-null (<i>Klf15-/-</i>) under fed vs. 48 hours fasting conditions, (n = 5), *P,0.05 vs. WT Fast. (B) Representative echocardiography image from WT vs. <i>Klf15-/-</i> following a 48 hour fast. (C) Tabular representation of echocardiography data in WT vs. <i>Klf15-/-</i> under fed vs. 48 hour fasting conditions.</p