Ketone Body Metabolism in the Ischemic Heart

Ketone bodies have been identified as an important, alternative fuel source in heart failure. In addition, the use of ketone bodies as a fuel source has been suggested to be a potential ergogenic aid for endurance exercise performance. These findings have certainly renewed interest in the use of ketogenic diets and exogenous supplementation in an effort to improve overall health and disease. However, given the prevalence of ischemic heart disease and myocardial infarctions, these strategies may not be ideal for individuals with coronary artery disease. Although research studies have clearly defined changes in fatty acid and glucose metabolism during ischemia and reperfusion, the role of ketone body metabolism in the ischemic and reperfused myocardium is less clear. This review will provide an overview of ketone body metabolism, including the induction of ketosis via physiological or nutritional strategies. In addition, the contribution of ketone body metabolism in healthy and diseased states, with a particular emphasis on ischemia-reperfusion (I-R) injury will be discussed

Assessment of Cardiac Function and Energetics in Isolated Mouse Hearts Using 31P NMR Spectroscopy

Bioengineered mouse models have become powerful research tools in determining causal relationships between molecular alterations and models of cardiovascular disease. Although molecular biology is necessary in identifying key changes in the signaling pathway, it is not a surrogate for functional significance. While physiology can provide answers to the question of function, combining physiology with biochemical assessment of metabolites in the intact, beating heart allows for a complete picture of cardiac function and energetics. For years, our laboratory has utilized isolated heart perfusions combined with nuclear magnetic resonance (NMR) spectroscopy to accomplish this task. Left ventricular function is assessed by Langendorff-mode isolated heart perfusions while cardiac energetics is measured by performing 31P magnetic resonance spectroscopy of the perfused hearts. With these techniques, indices of cardiac function in combination with levels of phosphocreatine and ATP can be measured simultaneously in beating hearts. Furthermore, these parameters can be monitored while physiologic or pathologic stressors are instituted. For example, ischemia/reperfusion or high workload challenge protocols can be adopted. The use of aortic banding or other models of cardiac pathology are apt as well. Regardless of the variants within the protocol, the functional and energetic significance of molecular modifications of transgenic mouse models can be adequately described, leading to new insights into the associated enzymatic and metabolic pathways. Therefore, 31P NMR spectroscopy in the isolated perfused heart is a valuable research technique in animal models of cardiovascular disease

Ketogenic Diets and Exercise Performance

The ketogenic diet (KD) has gained a resurgence in popularity due to its purported reputation for fighting obesity. The KD has also acquired attention as an alternative and/or supplemental method for producing energy in the form of ketone bodies. Recent scientific evidence highlights the KD as a promising strategy to treat obesity, diabetes, and cardiac dysfunction. In addition, studies support ketone body supplements as a potential method to induce ketosis and supply sustainable fuel sources to promote exercise performance. Despite the acceptance in the mainstream media, the KD remains controversial in the medical and scientific communities. Research suggests that the KD or ketone body supplementation may result in unexpected side effects, including altered blood lipid profiles, abnormal glucose homeostasis, increased adiposity, fatigue, and gastrointestinal distress. The purpose of this review article is to provide an overview of ketone body metabolism and a background on the KD and ketone body supplements in the context of obesity and exercise performance. The effectiveness of these dietary or supplementation strategies as a therapy for weight loss or as an ergogenic aid will be discussed. In addition, the recent evidence that indicates ketone body metabolism is a potential target for cardiac dysfunction will be reviewed

Sex Differences in Endurance Exercise Capacity and Skeletal Muscle Lipid Metabolism in Mice

Previous studies suggest that sex differences in lipid metabolism exist with females demonstrating a higher utilization of lipids during exercise, which is mediated partly by increased utilization of muscle triglycerides. However, whether these changes in lipid metabolism contribute directly to endurance exercise performance is unclear. Therefore, the objective of this study was to investigate the contribution of exercise substrate metabolism to sex differences in endurance exercise capacity (EEC) in mice. Male and female C57BL/6-NCrl mice were subjected to an EEC test until exhaustion on a motorized treadmill. The treadmill was set at a 10% incline, and the speed gradually increased from 10.2 m/min to 22.2 m/min at fixed intervals for up to 2.5 h. Tissues and blood were harvested in mice immediately following the EEC. A cohort of sedentary, non-exercised male and female mice were used as controls. Females outperformed males by ~25% on the EEC. Serum levels of both fatty acids and ketone bodies were ~50% higher in females at the end of the EEC. In sedentary female mice, skeletal muscle triglyceride content was significantly greater compared to sedentary males. Gene expression analysis demonstrated that genes involved in skeletal muscle fatty acid oxidation were significantly higher in females with no changes in genes associated with glucose uptake or ketone body oxidation. The findings suggest that female mice have a higher endurance exercise capacity and a greater ability to mobilize and utilize fatty acids for energy

The Effects of Exercise Training on Glucose Homeostasis and Muscle Metabolism in Type 1 Diabetic Female Mice

Although exercise training is an important recommendation for the management of type 1 diabetes (T1D), most of the available research studies predominantly focus on male subjects. Given the importance of sex as a biological variable, additional studies are required to improve the knowledge gap regarding sex differences in T1D research. Therefore, the purpose of this study was to examine the role of exercise training in mediating changes in glucose homeostasis and skeletal muscle metabolism in T1D female mice. Female mice were injected with streptozotocin (STZ) to induce T1D. Two weeks after STZ injection, control (CON) and STZ mice were exercise trained on a treadmill for 4 weeks. Aerobic exercise training failed to improve glucose tolerance, prevent the decrease in body weight and adipose tissue mass, or attenuate muscle atrophy in T1D female mice. However, insulin sensitivity was improved in T1D female mice after exercise training. Aerobic exercise training maintained skeletal muscle triglyceride content but did not prevent depletion of skeletal muscle or liver glycogen in T1D mice. Gene expression analysis suggested that T1D resulted in decreased glucose transport, decreased ketone body oxidation, and increased fatty acid metabolism in the skeletal muscle, which was not altered by exercise training. These data demonstrate that 4 weeks of aerobic exercise training of a moderate intensity is insufficient to counteract the negative effects of T1D in female mice, but does lead to an improvement in insulin sensitivity

Maharam-type kernel representation for operators with a trigonometric domination

[EN] Consider a linear and continuous operator T between Banach function spaces. We prove that under certain requirements an integral inequality for T is equivalent to a factorization of T through a specific kernel operator: in other words, the operator T has what we call a Maharam-type kernel representation. In the case that the inequality provides a domination involving trigonometric functions, a special factorization through the Fourier operator is given. We apply this result to study the problem that motivates the paper: the approximation of functions in L2[0, 1] by means of trigonometric series whose Fourier coefficients are given by weighted trigonometric integrals.This research has been supported by MTM2016-77054-C2-1-P (Ministerio de Economia, Industria y Competitividad, Spain).Sánchez Pérez, EA. (2017). Maharam-type kernel representation for operators with a trigonometric domination. Aequationes Mathematicae. 91(6):1073-1091. https://doi.org/10.1007/s00010-017-0507-6S10731091916Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Generalized perfect spaces. Indag. Math. 19(3), 359–378 (2008)Calabuig, J.M., Delgado, O., Sánchez Pérez, E.A.: Factorizing operators on Banach function spaces through spaces of multiplication operators. J. Math. Anal. Appl. 364, 88–103 (2010)Delgado, O., Sánchez Pérez, E.A.: Strong factorizations between couples of operators on Banach function spaces. J. Convex Anal. 20(3), 599–616 (2013)Dodds, P.G., Huijsmans, C.B., de Pagter, B.: Characterizations of conditional expectation type operators. Pacific J. Math. 141(1), 55–77 (1990)Flores, J., Hernández, F.L., Tradacete, P.: Domination problems for strictly singular operators and other related classes. Positivity 15(4), 595–616 (2011). 2011Fremlin, D.H.: Tensor products of Banach lattices. Math. Ann. 211, 87–106 (1974)Hu, G.: Weighted norm inequalities for bilinear Fourier multiplier operators. Math. Ineq. Appl. 18(4), 1409–1425 (2015)Halmos, P., Sunder, V.: Bounded Integral Operators on $$L^2$$ L 2 Spaces. Springer, Berlin (1978)Kantorovitch, L., Vulich, B.: Sur la représentation des opérations linéaires. Compositio Math. 5, 119–165 (1938)Kolwicz, P., Leśnik, K., Maligranda, L.: Pointwise multipliers of Calderón- Lozanovskii spaces. Math. Nachr. 286, 876–907 (2013)Kolwicz, P., Leśnik, K., Maligranda, L.: Pointwise products of some Banach function spaces and factorization. J. Funct. Anal. 266(2), 616–659 (2014)Kuo, W.-C., Labuschagne, C.C.A., Watson, B.A.: Conditional expectations on Riesz spaces. J. Math. Anal. Appl. 303, 509–521 (2005)Lindenstrauss, J., Tzafriri, L.: Classical Banach Spaces II. Springer, Berlin (1979)Maharam, D.: The representation of abstract integrals. Trans. Am. Math. Soc. 75, 154–184 (1953)Maharam, D.: On kernel representation of linear operators. Trans. Am. Math. Soc. 79, 229–255 (1955)Maligranda, L., Persson, L.E.: Generalized duality of some Banach function spaces. Indag. Math. 51, 323–338 (1989)Neugebauer, C.J.: Weighted norm inequalities for averaging operators of monotone functions. Publ. Mat. 35, 429–447 (1991)Okada, S., Ricker, W.J., Sánchez Pérez, E.A.: Optimal Domain and Integral Extension of Operators Acting in Function Spaces. Operator Theory: Adv. Appl., vol. 180. Birkhäuser, Basel (2008)Rota, G.C.: On the representation of averaging operators. Rend. Sem. Mat. Univ. Padova. 30, 52–64 (1960)Sánchez Pérez, E.A.: Factorization theorems for multiplication operators on Banach function spaces. Integr. Equ. Oper. Theory 80(1), 117–135 (2014)Schep, A.R.: Factorization of positive multilinear maps. Ill. J. Math. 28(4), 579–591 (1984)Schep, A.R.: Products and factors of Banach function spaces. Positivity 14(2), 301–319 (2010

Orthogonalities and functional equations

In this survey we show how various notions of orthogonality appear in the theory of functional equations. After introducing some orthogonality relations, we give examples of functional equations postulated for orthogonal vectors only. We show their solutions as well as some applications. Then we discuss the problem of stability of some of them considering various aspects of the problem. In the sequel, we mention the orthogonality equation and the problem of preserving orthogonality. Last, but not least, in addition to presenting results, we state some open problems concerning these topics. Taking into account the big amount of results concerning functional equations postulated for orthogonal vectors which have appeared in the literature during the last decades, we restrict ourselves to the most classical equations