**Preface to "Energy Metabolism and Diet"**

We have great pleasure in presenting this Special Issue of *Nutrients* on "Energy metabolism and diet". The scope of this issue is the complex interaction between diet, energy metabolism and health or physical functioning, and all of the contributions to this issue aim to increase our understanding of this interaction and how it can be applied to improve human health and, more specifically, metabolic health. This Special Issue is particularly valuable to any scientist or health professional working in the field of health, nutrition and exercise. It is acknowledged that this valuable contribution to this field of expertise could only be realized thanks to the high-quality contributions of the authors Ciara Cooney, Ed Daly, Maria McDonagh, Lisa Ryan, Emmanuel Rineau, Na¨ıg Gueguen, Vincent Procaccio, Franck Genevieve, Pascal Reynier, Daniel Henrion, Sigismond Lasocki, Gabriella Sistilli, ` Veronika Kalendova, Tomas Cajka, Illaria Irodenko, Kristina Bardova, Marina Oseeva, Petr Zacek, Petra Kroupova, Olga Horakova, Karoline Lackner, Amalia Gastaldelli, Ondrej Kuda, Jan Kopecky, Martin Rossmeisl, Rieneke Terink, Renger F. Witkamp, Maria T. E. Hopman, Els Siebelink, Huub F. J. Savelkoul, Marco Mensink, Jiri Funda, Radek Pohl, Tomas Cajka, Michal Hensler, Petra Janovska, Katerina Adamcova, Lucie Lenkova, Petr Zouhar, Pavel Flachs and Jerry Colca. Moreover, we are grateful to the editorial office of *Nutrients* for the assistance during the initiation and completion of this special issue.

> **Arie Nieuwenhuizen, Evert van Schothorst** *Editors*

### *Editorial* **Energy Metabolism and Diet**

**Arie G. Nieuwenhuizen \* and Evert M. van Schothorst** *Editorial*

evert.vanschothorst@wur.nl

Human and Animal Physiology, Wageningen University, 6708 WD Wageningen, The Netherlands; evert.vanschothorst@wur.nl **Energy Metabolism and Diet**

Human and Animal Physiology, Wageningen University, 6708 WD Wageningen, The Netherlands;

**\*** Correspondence: arie.nieuwenhuizen@wur.nl; Tel.: +31-317482760 **Arie G. Nieuwenhuizen \* and Evert M. van Schothorst**

> Energy metabolism at whole body and cellular, and even organelle (i.e., mitochondrial), level requires adequate regulation in order to maintain or improve (metabolic) health. In eukaryotic cells, mitochondria are key players in energy (ATP) production via oxidative phosphorylation. Both macro- and micronutrients potentially influence energy metabolism and mitochondrial functioning, either as substrates for (oxidative) catabolism or as essential constituents of enzymes or protein complexes involved in (mitochondrial) energy metabolism (Figure 1). **\*** Correspondence: arie.nieuwenhuizen@wur.nl; Tel.: +31-317482760 Energy metabolism at whole body and cellular, and even organelle (i.e., mitochondrial), level requires adequate regulation in order to maintain or improve (metabolic) health. In eukaryotic cells, mitochondria are key players in energy (ATP) production via oxidative phosphorylation. Both macro- and micronutrients potentially influence energy metabolism and mitochondrial functioning, either as substrates for (oxidative) catabolism or as essential constituents of enzymes or protein complexes involved in (mitochondrial) energy metabolism (Figure 1).

**Figure 1.** Schematic concept on the interaction between diet, energy metabolism, and health. **Figure 1.** Schematic concept on the interaction between diet, energy metabolism, and health.

In this issue, a range of new articles are presented, and we are fortunate to have a collection of empirical preclinical and human studies to assist in the development of understanding and progress in this area of research on improving health, and, in more detail, metabolic health. The studies in this Special Issue deal with various aspects of nutrition, as summarized below: In this issue, a range of new articles are presented, and we are fortunate to have a collection of empirical preclinical and human studies to assist in the development of understanding and progress in this area of research on improving health, and, in more detail, metabolic health. The studies in this Special Issue deal with various aspects of nutrition, as summarized below:

#### **Energy Balance Energy Balance**

[2].

**Specific Nutrients**

Focused on the topic of energy balance, Cooney and colleagues report findings of a weight loss study in ageing Irish adults with overweight and adiposity-based chronic disease [1]. Participants had dietary energy requirements prescribed on the basis of either measured resting metabolic rate (mRMR) or estimated RMR by the prediction of Miffin [1]. A similar weight loss (>5%) over the short-term period of 12 weeks was seen in these two groups, together with a reduction in blood pressure, triglycerides, and glucose, thus reducing cardiovascular disease risk factors. Cumulatively, these data further support the use of RMR, either measured or estimated, to determine energy intake during a weight loss program [1]. Focused on the topic of energy balance, Cooney and colleagues report findings of a weight loss study in ageing Irish adults with overweight and adiposity-based chronic disease [1]. Participants had dietary energy requirements prescribed on the basis of either measured resting metabolic rate (mRMR) or estimated RMR by the prediction of Miffin [1]. A similar weight loss (>5%) over the short-term period of 12 weeks was seen in these two groups, together with a reduction in blood pressure, triglycerides, and glucose, thus reducing cardiovascular disease risk factors. Cumulatively, these data further support the use of RMR, either measured or estimated, to determine energy intake during a weight loss program [1].

#### **Macronutrient Composition**

**Macronutrient Composition** In recreational athletes, Terink and colleagues elegantly showed, by using a crossover study where athletes consumed one of two diets in random order with a wash-out period of >2 weeks in between, that a low-carbohydrate, high-fat (LCHF) diet resulted in reduced workload with metabolic effects and a pronounced exercise-induced cortisol response after 2 days, when compared to a high-carbohydrate (HC) diet. Although indications of adaptation were seen after 2 weeks on the LCHF diet, work output was still lower In recreational athletes, Terink and colleagues elegantly showed, by using a cross-over study where athletes consumed one of two diets in random order with a wash-out period of >2 weeks in between, that a low-carbohydrate, high-fat (LCHF) diet resulted in reduced workload with metabolic effects and a pronounced exercise-induced cortisol response after 2 days, when compared to a high-carbohydrate (HC) diet. Although indications of adaptation were seen after 2 weeks on the LCHF diet, work output was still lower [2].

nandez

**Citation:** Nieuwenhuizen, A.G.; van Schothorst, E.M. Energy Metabolism and Diet. *Nutrients* **2021**, *13*, 1907. https://doi.org/10.3390/nu13061907 Metabolism and Diet. *Nutrients* **2021**, *13*, x. https://doi.org/10.3390/xxxxx Academic Editor(s): Maria Luz Fer-

Received: 25 May 2021 Accepted: 31 May 2021 Published: 1 June 2021 Received: date 25 May 2021 Accepted: date 31 May 2021

Published: date

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**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). **Copyright:** © 2021 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

*Nutrients* **2021**, *13*, x. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/nutrients

#### **Specific Nutrients**

Starting with the trace element iron, amongst others involved in oxidation–reduction reactions of energy metabolism, Rineau and colleagues focused on endurance capacity and fatigue, one of the main symptoms of iron deficiency [3]. They showed that iron deficiency without anemia in mice significantly reduced endurance and activity of the respiratory chain complex I in the predominantly slow-twitch musculus soleus, but not in the musculus quadriceps. This was seen without differences in complex IV activity in both muscles. They concluded that iron deficiency without anemia results in impaired mitochondrial complex I activity in skeletal muscles with predominantly oxidative metabolism, which might explain the observed reduction of fatigue and improved physical activity when correcting iron deficiency in humans [3].

In light of the increasing number of people with obesity and associated noncommunicable diseases nutritional approaches are highly warranted to combat developments of type 2 diabetes and the spectrum of conditions ranging from increased intrahepatic accumulation of triacylglycerols (fatty liver), hepatic steatosis, steatohepatitis (NASH) and end-stage liver disease,. Previously, it has been well reported that fish oils, and more specifically, the fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), contribute to health benefits, including, but not limited to, nonalcoholic fatty liver disease (NAFLD; reviewed by, e.g., Chang and colleagues (Prostaglandins Leukot. Essent. Fat. Acids, 2018). In this special issue, Sistilli and colleagues [4] and Bardova and colleagues [5] show some new insights revealing the nutritional power of these fatty acids as part of fish oil triglycerides or of krill oil (and its constituents), which includes high levels of phospholipids (PL) composed of a glycerol backbone with two fatty acids (either EPA or DHA) and a phosphate group modified with simple organic molecules such as choline, ethanolamine, or serine. Sistilli et al. showed impressive antisteatotic effects in the liver by krill oil versus fish oil using an obese, insulin-resistant mouse model of exacerbated NAFLD based on high-fat feeding at thermoneutral temperature. Moreover, effects were seen in both the prevention and reversal of hepatic steatosis. This was associated with improved hepatic insulin sensitivity and high plasma adiponectin levels [4].

Bardova et al., in contrast, investigated potential additive effects by combining nutritional and pharmacological interventions, using fish oil together with a first- or secondgeneration antidiabetic drug, thiazolidinedione (TZD). Focusing on white adipose tissue, increased fatty acid futile cycling (triacylglycerols → free fatty acids + glycerol → triacylglycerols) supporting energy dissipation was seen as an additive beneficial effect of fish oil and TZDs, together with increased metabolic health in these diet-induced obese mice. This included reduced body weight gain, and improvements in circulating and tissue metabolites and parameters of both lipid and glucose homeostasis [5].

Together, the studies of this Special Issue provide novel detailed insights into the physiological nature of the close relationship between (nutrients) our diet, energy metabolism, and physical functioning, and confirm the importance of this relationship for maintaining good health.

**Author Contributions:** A.G.N. and E.M.v.S. conceptualized and co-wrote this article. Both authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** Not applicable.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

