Rat models of diet-induced obesity and metabolic dysregulation: Current trends, shortcomings and considerations for future research.

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.

Characterization and Comparison of the Divergent Metabolic Consequences of High-Sugar and High-Fat Diets in Male Wistar Rats.

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.

Physical Exercise Potentially Targets Epicardial Adipose Tissue to Reduce Cardiovascular Disease Risk in Patients with Metabolic Diseases: Oxidative Stress and Inflammation Emerge as Major Therapeutic Targets.

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.

A systematic review exploring the significance of measuring epicardial fat thickness in correlation to B-type natriuretic peptide levels as prognostic and diagnostic markers in patients with or at risk of heart failure.

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.

Is Adipose Tissue the Fountain of Youth? The Impact of Adipose Stem Cell Aging on Metabolic Homeostasis, Longevity, and Cell-Based Therapies.

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.

An In Vivo/Ex Vivo Study Design to Investigate Effects of Chronic Conditions and Therapeutic Compounds on Adipose Stem Cells in Animal Models.

With the dramatic rise in the global prevalence of obesity and lack of success at addressing this public health issue, there is an urgency to develop new tools with which to study obesity and putative weight-loss products. Pre-adipocyte cell lines have been widely used as a model for adipocyte biology and obesity over the past four decades, but the applicability of results from these cell lines is limited. This chapter will describe an in vivo/ex vivo study design that can be employed to examine the effects of diets and other chronic physiological or pathophysiological conditions on the biology of adipose stem cells (ASCs), as a model for the progression and management of obesity.

Modulation of Glucose Metabolism by Leaf Tea Constituents: A Systematic Review of Recent Clinical and Pre-clinical Findings.

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 teas) were included, with mixed results, and providing scant mechanistic information.

The Regulation of Marrow Fat by Vitamin D: Molecular Mechanisms and Clinical Implications.

Purpose Of Review: To review the available literature regarding a possible relationship between vitamin D and bone marrow adipose tissue (BMAT), and to identify future avenues of research that warrant attention.

Recent Findings: Results from in vivo animal and human studies all support the hypothesis that vitamin D can suppress BMAT expansion. This is achieved by antagonizing adipogenesis in bone marrow stromal cells, through inhibition of PPARγ2 activity and stimulation of pro-osteogenic Wnt signalling.

The Effect of Vancomycin on the Viability and Osteogenic Potential of Bone-Derived Mesenchymal Stem Cells.

Traditionally, methicillin-resistant Staphylococcus aureus (MRSA) is treated with vancomycin, administrated intravenously or applied directly onto infected tissue. The effect of direct (as opposed to systemic) vancomycin treatment on bone formation and remodelling is largely unknown. The minimal inhibitory concentration (MIC) of vancomycin was determined by adding 200 μL of different concentrations (1-20 μg/mL) to actively growing cultures of S.

Adipocyte biology: It is time to upgrade to a new model.

Globally, the obesity pandemic is profoundly affecting quality of life and economic productivity, but efforts to address this, especially on a pharmacological level, have generally proven unsuccessful to date, serving as a stark demonstration that our understanding of adipocyte biology and pathophysiology is incomplete. To deliver better insight into adipocyte function and obesity, we need improved adipocyte models with a high degree of fidelity in representing the in vivo state and with a diverse range of experimental applications. Adipocyte cell lines, especially 3T3-L1 cells, have been used extensively over many years, but these are limited in terms of relevance and versatility.

Vanadate Impedes Adipogenesis in Mesenchymal Stem Cells Derived from Different Depots within Bone.

Glucocorticoid-induced osteoporosis (GIO) is associated with an increase in bone marrow adiposity, which skews the differentiation of mesenchymal stem cell (MSC) progenitors away from osteoblastogenesis and toward adipogenesis. We have previously found that vanadate, a non-specific protein tyrosine phosphatase inhibitor, prevents GIO in rats, but it was unclear whether vanadate directly influenced adipogenesis in bone-derived MSCs. For the present study, we investigated the effect of vanadate on adipogenesis in primary rat MSCs derived from bone marrow (bmMSCs) and from the proximal end of the femur (pfMSCs).

Free fatty acid G-protein coupled receptor signaling in M1 skewed white adipose tissue macrophages.

Obesity is associated with the establishment and maintenance of a low grade, chronically inflamed state in the white adipose tissue (WAT) of the body. The WAT macrophage population is a major cellular participant in this inflammatory process that significantly contributes to the pathophysiology of the disease, with the adipose depots of obese individuals, relative to lean counterparts, having an elevated number of macrophages that are skewed towards a pro-inflammatory phenotype. Alterations in the WAT lipid micro-environment, and specifically the availability of free fatty acids, are believed to contribute towards the obesity-related quantitative and functional changes observed in these cells.

The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts.

Glucocorticoid (GC)-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs) and ADSC-derived pre-osteoblasts (ADSC-OBs).

Depot-specific and hypercaloric diet-induced effects on the osteoblast and adipocyte differentiation potential of adipose-derived stromal cells.

Adipose-derived stromal cells (ADSCs) can be differentiated in vitro into several mesenchyme-derived cell types. We had previously described depot-specific differences in the adipocyte differentiation of ADSCs, and consequently we hypothesized that there may also be depot-specific differences in osteoblast differentiation of ADSCs. For this study, the osteoblast differentiation potential of rat subcutaneous ADSCs (scADSCs) and perirenal visceral ADSCs (pvADSCs) was compared.

Genomic and nongenomic cross talk between the gonadotropin-releasing hormone receptor and glucocorticoid receptor signaling pathways.

The GnRH receptor (GnRHR), a member of the G protein-coupled receptor family, is a central regulator of reproductive function in all vertebrates. The peptide hormone GnRH exerts its effects via binding to the GnRHR in pituitary gonadotropes. We investigated the mechanisms of regulation of transcription of the mGnRHR gene in the mouse pituitary gonadotrope L beta T2 cell line by GnRH and dexamethasone (dex).