Metabolism revisited

Abstract

Metabolism, disrupted metabolic function, and the pathophysiology of aberrant body weight states are classics of physiological research and non-negotiables in most medical school curricula. Let us quickly revisit current topics in this wide area, stay up to date, and have a look at recently published articles in Acta Physiologica.

Dietary strategies are usually the first and most recommended lifestyle adaptations in the management of metabolic syndrome, high triglycerides, and low HDL cholesterol, including a recommended primary intake of complex carbs, proteins, and monounsaturated fats, mainly from plant-based sources.¹ Metabolic syndrome spectrum pathophysiology is characterized by a reduced metabolic reserve and flexibility, that is, an impaired ability to adequately respond to changing metabolic demands, as is the case in insulin resistance and impaired fuel selection between glucose and fatty acids in obesity and type 2 diabetes, respectively.² Kutz et al.³ recently elucidated the role of Na/K-ATPase (NKA)-mediated regulation of Src kinase in the regulation of metabolic capacity, which can, interestingly, be targeted pharmacologically. Dos Santos et al.⁴ investigate the influence of macronutrient on the insulin-to-glucagon ratio in healthy and diabetic individuals, which is a more sufficient parameter than either insulin or glucagon levels alone.⁵ Their results are in favor of the low-carb approach to weight loss in overweight individuals. Another interesting observation comes from a study done by Popov et al., who showed how a high-fat diet, which is in other context considered harmful, actually enhances the size and function of astrocytes and promotes synaptic plasticity,⁶ thus leaving the scientific community with a lot of food for thought, as to, for example, in which contexts dietary-induced changes in astrocytic morphology and function would be beneficial or detrimental.⁷ Desmet et al., in a recent study, describe how chronic jetlag, as occurs frequent time zone traveling, actually disrupts rhythmicity in gut function, with potential negative metabolic consequences, for example, an alteration of the food intake pattern and involuntary body weight gain.⁸ Shibayama et al. recently investigated how hepatic glucocorticoid receptors are stabilized during starvation periods, an important step in elucidating the transcriptional control of nuclear receptors in physiological fasting-feeding cycles.⁹

Exercise regimens are another staple in the international guidelines for the long-term management of metabolic syndrome.¹⁰ In a recent study by Sabaratnam et al., the role of the skeletal muscle as an endocrine organ is recognized, in, for example, exercise-mediated interorgan communication through myokine release.¹¹ Given the differences in skeletal muscle function between subjects of different ages or gender,¹² the study of metabolic effects of muscle tissue needs to differentiate accordingly. Christiansen et al. have seen first indications of an added benefit of controlled blood flow restriction in exercise-mediated induction of factors regulating cholesterol production and glucose homeostasis.¹³ Marafon et al. investigated the influence of different exercise regimen patterns on endoplasmic reticulum stress markers in skeletal muscle, showing that, while chronic exercise attenuates ER stress, acute exercise requires adequate recovery periods to avoid pathophysiologic induction of ER stress, with subsequent metabolic consequences.¹⁴ Loss of muscle mass, which can be due to several different pathophysiologic mechanisms, has relatively recently been shown to be a novel risk factor for cardiovascular disease. Even without a reduction in body mass, exercise, via an increase in skeletal muscle tissue volume, may protect against obesity-related secondary cardiovascular dysfunction such as hypertension and secondary renal injury.¹⁵ We are only recently beginning to unravel the complex interaction of hypertension, loss of muscle volume, and CV risk in different systemic diseases.^{16, 17} Myokine networks regulate the complex mechanisms required to regenerate skeletal muscle in attempts to counteract the effects of a loss of volume in skeletal muscle tissue.¹⁸ Doncheva et al. have found first evidence of extracellular vesicles, also mediators in interorgan cross talk, change in association with exercise, and impact metabolic health such as obesity and insulin sensitivity.¹⁹

Studies of metabolic aberrations in humans would not be complete without considering metabolic interactions between parental and filial generations. Recently, Cornejo et al. described how pre-pregnancy obesity, a condition which is on the rise worldwide, affects the vascular aberrations and resulting risk for both the mother and the foetus in gestational diabetes.²⁰ Lean et al. have taken a closer look at the negative effects of obesity on maternal lactation ability,²¹ another obesity-associated complication in childbearing women that warrants early vigilance and targeted intervention.

Taken together, while most of these findings suggest an increase in a multitude of obesity-associated health problems, the mechanisms outlined in these studies help develop targeted strategies for prevention and therapeutic intervention.

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