**Cristiano Capurso**

Cristiano Capurso is currently working as Associate Professor at the Department of Surgical and Medical Sciences of the University of Foggia, Italy. He holds a medical degree and a specialization in Geriatric Medicine from the University of Bari, Italy. She also holds a PhD in Carcinogenesis, Aging and Immunoregulation from the University of Bari, Italy. His research interests include cognitive decline, hyperlipidaemia, atherosclerosis, diet pattern, i.e., the Mediterranean Diet, and markers for human longevity. He has more two decades of experience in these fields. He has published approximately 129 papers in peer-reviewed journals. He has also collaborated with other researchers to publish a scientific book in English with Springer and a chapter of the volume "Principles of Nutrigenetics and Nutrigenomics" with Elsevier. He is a member of the Italian Society of Gerontology and Geriatrics, of the Italian Society for the Study of Atherosclerosis, and of Italian Society of Internal Medicine.

#### **Catherine F ´eart**

Catherine Feart is currently working as tenured researcher at the Bordeaux Population Health ´ research center of the INSERM, University of Bordeaux, France. She holds a PhD in Nutrition and Food Sciences, and a Qualification to Direct Researches (HDR) in Public Health and Epidemiology. Her research focuses on the relationship between nutrition and food intake and the onset of geriatric syndromes, using the tools of the nutritional epidemiology field. She is mainly interested in the potential benefit of specific nutrients, foods and dietary patterns on the risk of developing mental disorders, including dementia and depression, and physical frailty and by the underlying mechanisms, including the role of gu<sup>t</sup> microbiota and inflammation on these relationships. She has published around 120 papers (original articles and reviews) in peer-reviewed journals. She is a member of the steering committees of the French Society of Nutrition (SFN) and of the Group Lipids and Nutrition (GLN) and is the leader of the University Diploma (DU) Nutritional epidemiology via the internet at the University of Bordeaux.

#### **Preface to "Nutrition, Diet Quality, Aging and Frailty"**

In the last century, the average life expectancy at birth increased from roughly 45 years in the early 1900s to more than 80 years of age at present. However, living longer is often related to different levels of frailty. There is no curative treatment for frailty—the interventions that have been described as effective to slow or delay the onset of frailty are physical activity and nutritional interventions. Maintaining adequate nutrition status is important to reduce the risk of chronic diseases, many of which are age-related. On the other hand, frailty itself may have a negative effect on eating and, thus, on the nutritional status.

The main goal of this Special Issue is to address existing knowledge on nutrition regarding the causative factors of frailty and disease due to aging, i.e., strategies for delaying the pathological effects of aging.

Published articles cover original research, protocol development, methodological studies, narrative or systematic reviews, and meta-analyses regarding the role of dietary patterns and the different aspects of frailty, from reduced muscle mass and strength to cognitive function, to impaired autonomy, or the slowing of aging. In addition, the articles published are concerned with the role of specific elements, such as albumin, homocysteine, fatty acids, and dairy products, in the different aspects of frailty and aging in cohort studies and animal models.

Beyond this Special Issue, of course, there remains a need for further research to address the multiple factors that determine longevity and aging, which naturally also involve nutrition.

Finally, we would like to express our most profound appreciation to the MDPI Book staff, the editorial team of Nutrients journal, the Assistant Editor of this Special Issue Ms. Stella Duo, the Managing Editor Ms. Chloe Wang, and all authors and the hardworking and professional reviewers.

> **Cristiano Capurso and Catherine F´eart** *Editors*

*Article*

## **Metabolic Defects Caused by High-Fat Diet Modify Disease Risk through Inflammatory and Amyloidogenic Pathways in a Mouse Model of Alzheimer's Disease**

#### **Austin M. Reilly 1, Andy P. Tsai 1, Peter B. Lin 1, Aaron C. Ericsson 2, Adrian L. Oblak 1 and Hongxia Ren 1,3,4,5,6,7,\*,**†


Received: 31 August 2020; Accepted: 25 September 2020; Published: 29 September 2020

**Abstract:** High-fat diet (HFD) has been shown to accelerate Alzheimer's disease (AD) pathology, but the exact molecular and cellular mechanisms remain incompletely understood. Moreover, it is unknown whether AD mice are more susceptible to HFD-induced metabolic dysfunctions. To address these questions, we used 5xFAD mice as an Alzheimer's disease model to study the physiological and molecular underpinning between HFD-induced metabolic defects and AD pathology. We systematically profiled the metabolic parameters, the gu<sup>t</sup> microbiome composition, and hippocampal gene expression in 5xFAD and wild type (WT) mice fed normal chow diet and HFD. HFD feeding impaired energy metabolism in male 5xFAD mice, leading to increased locomotor activity, energy expenditure, and food intake. 5xFAD mice on HFD had elevated circulating lipids and worsened glucose intolerance. HFD caused profound changes in gu<sup>t</sup> microbiome compositions, though no di fference between genotype was detected. We measured hippocampal mRNAs related to AD neuropathology and neuroinflammation and showed that HFD elevated the expression of apoptotic, microglial, and amyloidogenic genes in 5xFAD mice. Pathway analysis revealed that di fferentially regulated genes were involved in insulin signaling, cytokine signaling, cellular stress, and neurotransmission. Collectively, our results showed that 5xFAD mice were more susceptible to HFD-induced metabolic dysregulation and sugges<sup>t</sup> that targeting metabolic dysfunctions can ameliorate AD symptoms via e ffects on insulin signaling and neuroinflammation in the hippocampus.

**Keywords:** diet; metabolism; nutrient; glucose; lipid; insulin; neuroinflammation; Alzheimer's disease
