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Rat diet-induced obesity and metabolic dysregulation (DIO/DIMD) is widely used as a pre-clinical model for human obesity and for testing weight-loss interventions. The aim of this review was to utilise a systematic literature survey of rat DIO/DIMD studies as a tool to document trends around study design and metabolic outcomes of these studies, and to consider ways in which the design of these studies may be improved to enhance the relevance thereof for human obesity research. In total, 110 comparisons between control and obesogenic dietary groups were included in the survey. Young male rats were found to be the model of choice, but fewer than 50% of studies provided comprehensive information about diet composition and energy intake. In addition, it was found that the majority of expected DIO/DIMD responses (hyperglycemia, hyperinsulinemia, dyslipidemia, hypoadiponectinemia) occurred at < 80% frequency, drawing into question the concept of a "typical" or "appropriate" response. We discuss the impact of differences in diet composition and energy intake on metabolic outcomes against the context of large heterogeneity of obesogenic diets employed in rat DIO/DIMD studies, and provide recommendations for the improvement of reporting standards around diet composition and dietary intake. In addition, we highlight the lack of data from female and older rats and describe considerations around the inclusion of sex and age as a variable in rat DIO/DIMD studies, aiming towards improving the applicability of these studies as a model of human obesity, which is most prevalent in women and older individuals., Competing Interests: Declaration of Competing Interest The authors, H Sadie-Van Gijsen and LM Kotze-Hörstmann, declare that they have no conflicting interests., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The status of industrial Medicinal Chemistry was discussed with European Medicinal Chemistry Leaders from large to mid-sized pharma and CRO companies as well as biotechs. The chemical modality space has expanded recently from small molecules to address new challenging targets. Besides the classical SAR/SPR optimization of drug molecules also their 'greenness' has increasing importance. The entire pharma discovery ecosystem has developed significantly. Beyond pharma and academia new key players such as Biotech and integrated CROs as well as Digital companies have appeared and are now to a large extend fueled by VC money. Digitalization is happening everywhere but surprisingly did not change speed and success rates of projects so far. Future Medicinal Chemists will still have to be excellent synthetic chemists but in addition they must be knowledgeable in new computational areas such as data sciences. Their ability to collaborate and to work in teams is key., (© 2023 Wiley-VCH GmbH.)

Diet-induced obesity (DIO) in laboratory rodents can serve as a model with which to study the pathophysiology of obesity, but obesogenic diets (high-sugar and/or high-fat) are often poorly characterised and simplistically aimed at inducing metabolic derangements for the purpose of testing the therapeutic capacity of natural products and other bioactive compounds. Consequently, our understanding of the divergent metabolic responses to different obesogenic diet formulations is limited. The aim of the present study was to characterise and compare differences in the metabolic responses induced by low-fat, medium-fat/high-sugar and high-fat diets in rats through multivariate statistical modelling. Young male Wistar rats were randomly assigned to CON (laboratory chow, low-fat), OB1 (high-sugar, medium-fat) or OB2 (high-fat) dietary groups ( n = 24 each) for 17 weeks, after which metabolic responses were characterised. Projection-based multivariate analyses (principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA)) were used to explore the associations between measures of body composition and metabolism. Furthermore, we conducted a systematic literature survey to examine reporting trends in rat dietary intervention studies, and to determine how the metabolic responses observed in the present study compared to other recently published studies. The OB1 and OB2 dietary regimens resulted in distinct metabolic profiles, with OB1 characterised by perturbations in insulin homeostasis and adipose tissue secretory function, while OB2 was characterised by altered lipid and liver metabolism. This work therefore confirms, by means of direct comparison, that differences in dietary composition have a profound impact on metabolic and pathophysiological outcomes in rodent models of DIO. However, through our literature survey we demonstrate that dietary composition is not reported in the majority of rat dietary intervention studies, suggesting that the impact of dietary composition is often not considered during study design or data interpretation. This hampers the usefulness of such studies to provide enhanced mechanistic insights into DIO, and also limits the translatability of such studies within the context of human obesity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kotzé-Hörstmann, Cois, Johnson, Mabasa, Shabalala, Van Jaarsveld and Sadie-Van Gijsen.)

Emerging evidence suggests that epicardial fat thickness (EFT) may be a critical feature to understand cardiac health and determine the risk of heart failure. The current review critically assesses and discusses evidence on the efficiency of measuring EFT, in comparison to the well-known markers B-type natriuretic peptide (BNP) and its N-terminal fragment pro-B-type natriuretic peptide (NT-proBNP), as a prognostic and diagnostic approach in individuals with or at risk of heart failure. A systematic approach was undertaken to search major databases, PubMed, Scopus, Google Scholar and the Cochrane library to identify studies that quantified EFT and serum BNP/NT-proBNP levels in individuals with or at risk of heart failure. Twelve studies met the inclusion criteria and a total of 1983 participants were included in this systematic review. Evidence shows a clear association between increased EFT and elevated BNP/NT-proBNP levels in individuals with metabolic disease and suggests that both methods can be used for heart failure diagnosis and prognosis. However, due to the broad spectrum of challenges linked with measuring EFT, BNP/Pro-BNP is the predominant method used for heart failure diagnosis and prognosis in clinical practice. Nonetheless, measuring EFT provides a powerful and reproducible diagnostic tool for risk stratification and heart failure diagnosis and prognosis. Importantly, measuring EFT proves valuable to validate BNP/NT-proBNP levels to predict heart failure, especially due to its non-invasive nature., (© 2021. The Author(s).)

Excess epicardial adiposity, within a state of obesity and metabolic syndrome, is emerging as an important risk factor for the development of cardiovascular diseases (CVDs). Accordingly, increased epicardial fat thickness (EFT) implicates the exacerbation of pathological mechanisms involving oxidative stress and inflammation within the heart, which may accelerate the development of CVDs. This explains increased interest in targeting EFT reduction to attenuate the detrimental effects of oxidative stress and inflammation within the setting of metabolic syndrome. Here, we critically discuss clinical and preclinical evidence on the impact of physical exercise on EFT in correlation with reduced CVD risk within a setting of metabolic disease. This review also brings a unique perspective on the implications of oxidative stress and inflammation as major pathological consequences that link increased EFT to accelerated CVD risk in conditions of metabolic disease.

Aging is driven by four interlinked processes: (1) low-grade sterile inflammation; (2) macromolecular and organelle dysfunction, including DNA damage, telomere erosion, and mitochondrial dysfunction; (3) stem cell dysfunction; and (4) an accumulation of senescent cells in tissues. Adipose tissue is not immune to the effects of time, and all four of these processes contribute to a decline of adipose tissue function with advanced age. This decline is associated with an increase in metabolic disorders. Conversely, optimally functioning adipose tissue generates signals that promote longevity. As tissue-resident progenitor cells that actively participate in adipose tissue homeostasis and dysregulation, adipose stem cells (ASCs) have emerged as a key feature in the relationship between age and adipose tissue function. This review will give a mechanistic overview of the myriad ways in which age affects ASC function and, conversely, how ASC function contribute to healthspan and lifespan. A central mediator in this relationship is the degree of resilience of ASCs to maintain stemness into advanced age and the consequent preservation of adipose tissue function, in particular subcutaneous fat. The last sections of this review will discuss therapeutic options that target senescent ASCs to extend healthspan and lifespan, as well as ASC-based therapies that can be used to treat age-related pathologies, and collectively, these therapeutic applications may transform the way we age.

Leaf teas are widely used as a purported treatment for dysregulated glucose homeostasis. The objective of this study was to systematically evaluate the clinical and cellular-metabolic evidence, published between January 2013 and May 2019, and indexed on PubMed, ScienceDirect, and Web of Science, supporting the use of leaf teas for this purpose. Fourteen randomized controlled trials (RCTs) (13 on Camellia sinensis teas) were included, with mixed results, and providing scant mechanistic information. In contrast, 74 animal and cell culture studies focusing on the pancreas, liver, muscle, and adipose tissue yielded mostly positive results and highlighted enhanced insulin signaling as a recurring target associated with the effects of teas on glucose metabolism. We conclude that more studies, including RCTs and pre-clinical studies examining teas from a wider variety of species beyond C. sinensis , are required to establish a stronger evidence base on the use of leaf teas to normalize glucose metabolism.