Shortened sleep duration impairs adipose tissue adrenergic stimulation of lipolysis in postmenopausal women.

Objective: The objective of this study was to examine the changes in adipose tissue lipolytic capacity and insulin signaling in response to shortened sleep duration (SSD) in postmenopausal women.

Methods: Adipose tissue from a randomized crossover study of nine healthy postmenopausal women (mean [SD], age: 59 [4] years; BMI: 28.0 [2.

Mapping lipid species remodeling in high fat diet-fed mice: Unveiling adipose tissue dysfunction with Raman microspectroscopy.

Dysregulated lipid metabolism in obesity leads to adipose tissue expansion, a major contributor to metabolic dysfunction and chronic disease. Lipid metabolism and fatty acid changes play vital roles in the progression of obesity. In this proof-of-concept study, Raman techniques combined with histochemical imaging methods were utilized to analyze the impact of a high-fat diet (HFD) on different types of adipose tissue in mice, using a small sample size (n = 3 per group).

Distribution and Sequestration of Cercosporin by cf. .

Plant-pathogenic fungi produce toxins as virulence factors in many plant diseases. In Cercospora leaf blight of soybean caused by cf. , symptoms are a consequence of the production of a perylenequinone toxin, cercosporin, which is light-activated to produce damaging reactive oxygen species.

Accelerated onset of diabetes in non-obese diabetic mice fed a refined high-fat diet.

Aim: Type 1 diabetes results from autoimmune events influenced by environmental variables, including changes in diet. This study investigated how feeding refined versus unrefined (aka 'chow') diets affects the onset and progression of hyperglycaemia in non-obese diabetic (NOD) mice.

Methods: Female NOD mice were fed either unrefined diets or matched refined low- and high-fat diets.

Multimodal Imaging of Pancreatic Cancer Microenvironment in Response to an Antiglycolytic Drug.

Lipid metabolism and glycolysis play crucial roles in the progression and metastasis of cancer, and the use of 3-bromopyruvate (3-BP) as an antiglycolytic agent has shown promise in killing pancreatic cancer cells. However, developing an effective strategy to avoid chemoresistance requires the ability to probe the interaction of cancer drugs with complex tumor-associated microenvironments (TAMs). Unfortunately, no robust and multiplexed molecular imaging technology is currently available to analyze TAMs.

Extract of L. Modulates Osteoblast Proliferation and Mineralization.

Thiazolidinediones (TZD) significantly improve insulin sensitivity via action on adipocytes. Unfortunately, TZDs also degrade bone by inhibiting osteoblasts. An extract of L.

NOD mice have distinct metabolic and immunologic profiles when compared with genetically similar MHC-matched ICR mice.

Nonobese diabetic (NOD) mice are the most commonly used rodent model to study mechanisms relevant to the autoimmunity and immunology of type 1 diabetes. Although many different strains of mice have been used as controls for studies comparing nondiabetic lines to the NOD strain, we hypothesized that the parental strain that gave rise to the NOD line might be one of the best options. Therefore, we compared female ICR and NOD mice, which are matched at key major histocompatibility complex (MHC) loci, to understand their metabolic and immunologic similarities and differences.

Aberrant lipid accumulation in the mouse visceral yolk sac resulting from maternal diabetes and obesity.

Maternal diabetes and obesity in pregnancy are well-known risk factors for structural birth defects, including neural tube defects and congenital heart defects. Progeny from affected pregnancies are also predisposed to developing cardiometabolic disease in later life. Based upon embryo cultures of rat embryos, it was postulated that nutrient uptake by the yolk sac is deficient in diabetic pregnancies.

Adipocyte-Specific Laminin Alpha 4 Deletion Preserves Adipose Tissue Health despite Increasing Adiposity.

Laminins are heterotrimeric glycoproteins with structural and functional roles in basement membranes. The predominant laminin alpha chain found in adipocyte basement membranes is laminin α4 (LAMA4). Global LAMA4 deletion in mice leads to reduced adiposity and increased energy expenditure, but also results in vascular defects that complicate the interpretation of metabolic data.

ICAM-1 Abundance Is Increased in Pancreatic Islets of Hyperglycemic Female NOD Mice and Is Rapidly Upregulated by NF-κB in Pancreatic β-Cells.

Type 1 diabetes (T1D) is classified as an autoimmune disease where pancreatic β-cells are specifically targeted by cells of the immune system. The molecular mechanisms underlying this process are not completely understood. Herein, we identified that the Icam1 gene and ICAM-1 protein were selectively elevated in female NOD mice relative to male mice, fitting with the sexual dimorphism of diabetes onset in this key mouse model of T1D.

FGF21 is required for protein restriction to extend lifespan and improve metabolic health in male mice.

Dietary protein restriction is increasingly recognized as a unique approach to improve metabolic health, and there is increasing interest in the mechanisms underlying this beneficial effect. Recent work indicates that the hormone FGF21 mediates the metabolic effects of protein restriction in young mice. Here we demonstrate that protein restriction increases lifespan, reduces frailty, lowers body weight and adiposity, improves physical performance, improves glucose tolerance, and alters various metabolic markers within the serum, liver, and adipose tissue of wildtype male mice.

Organization of sympathetic innervation of interscapular brown adipose tissue in the mouse.

The interscapular brown adipose tissue (iBAT) is under sympathetic control, and recent studies emphasized the importance of efferent sympathetic and afferent sensory or humoral feedback systems to regulate adipose tissue function and overall metabolic health. However, functional studies of the sympathetic nervous system in the mouse are limited, because details of anatomy and fine structure are lacking. Here, we used reporter mice for tyrosine hydroxylase expressing neurons (TH:tomato mice), iDISCO tissue clearance, confocal, lightsheet, and electron microscopy to clarify that (a) iBAT receives sympathetic input via dorsal rami (instead of often cited intercostal nerves); (b) dorsal rami T1-T5 correspond to the postganglionic input from sympathetic chain ganglia (stellate/T1-T5); (c) dorsal rami serve as conduits for sympathetic axons that branch off in finer nerve bundles to enter iBAT; (d) axonal varicosities show strong differential innervation of brown (dense innervation) versus white (sparse innervation) adipocytes, that surround the core iBAT in the mouse and are intermingled in human adipose tissues, (e) axonal varicosities can form neuro-adipocyte junctions with brown adipocytes.

Pioglitazone Reverses Markers of Islet Beta-Cell De-Differentiation in Mice While Modulating Expression of Genes Controlling Inflammation and Browning in White Adipose Tissue from Insulin-Resistant Mice and Humans.

Obesity, insulin resistance, and type 2 diabetes contribute to increased morbidity and mortality in humans. The mouse is an important mouse model that displays many key features of the human disease. Herein, we used the drug pioglitazone, a thiazolidinedione with insulin-sensitizing properties, to investigate blood glucose levels, indicators of islet β-cell health and maturity, and gene expression in adipose tissue.

Sympathetic innervation of the mouse kidney and liver arising from prevertebral ganglia.

The sympathetic nervous system (SNS) plays a crucial role in the regulation of renal and hepatic functions. Although sympathetic nerves to the kidney and liver have been identified in many species, specific details are lacking in the mouse. In the absence of detailed information of sympathetic prevertebral innervation of specific organs, selective manipulation of a specific function will remain challenging.

Perioperative Statin Use May Reduce Postoperative Arrhythmia Rates After Total Joint Arthroplasty.

Background: Postoperative arrhythmias are associated with increased morbidity and mortality in total joint arthroplasty (TJA) patients. HMG-CoA (3-hydroxy-3-methyl-glutaryl-CoA) reductase inhibitors (statins) decrease atrial fibrillation rates after cardiac surgery, but it is unknown if this cardioprotective effect is maintained after joint reconstruction surgery. We aim to determine if perioperative statin use decreases the incidence of 90-day postoperative arrhythmias in patients undergoing primary TJA.

Characterization of fibrillar collagen isoforms in infarcted mouse hearts using second harmonic generation imaging.

We utilized collagen specific second harmonic generation (SHG) signatures coupled with correlative immunofluorescence imaging techniques to characterize collagen structural isoforms (type I and type III) in a murine model of myocardial infarction (MI). Tissue samples were imaged over a four week period using SHG, transmitted light microscopy and immunofluorescence imaging using fluorescently-labeled collagen antibodies. The post-mortem cardiac tissue imaging using SHG demonstrated a progressive increase in collagen deposition in the left ventricle (LV) post-MI.

The Ubiquitin Ligase SIAH2 Negatively Regulates Glucocorticoid Receptor Activity and Abundance.

Glucocorticoids are clinically essential drugs used routinely to control inflammation. However, a host of metabolic side effects manifests upon usage beyond a few days. In the present study, we tested the hypothesis that seven-in-absentia mammalian homolog-2 (SIAH2), a ubiquitin ligase that regulates adipogenesis, is important for controlling adipocyte size, inflammation, and the ability of adipose tissue to expand in response to a glucocorticoid challenge.

Pancreatic, but not myeloid-cell, expression of interleukin-1alpha is required for maintenance of insulin secretion and whole body glucose homeostasis.

Objective: The expression of the interleukin-1 receptor type I (IL-1R) is enriched in pancreatic islet β-cells, signifying that ligands activating this pathway are important for the health and function of the insulin-secreting cell. Using isolated mouse, rat, and human islets, we identified the cytokine IL-1α as a highly inducible gene in response to IL-1R activation. In addition, IL-1α is elevated in mouse and rat models of obesity and Type 2 diabetes.

SIAH2 is Expressed in Adipocyte Precursor Cells and Interacts with EBF1 and ZFP521 to Promote Adipogenesis.

Objective: Expression of zinc finger protein 423 (ZFP423), a key proadipogenic transcription factor in adipocyte precursor cells, is regulated by interaction of the proadipogenic early B-cell factor 1 (EBF1) and antiadipogenic ZFP521. The ubiquitin ligase seven-in-absentia homolog 2 (SIAH2) targets ZFP521 for degradation. This study asked whether SIAH2 is expressed in adipocyte precursor cells and whether SIAH2 interacts with ZFP521 and EBF1 to regulate ZFP521 protein levels during adipogenesis.

Dietary Methionine Restriction Signals to the Brain Through Fibroblast Growth Factor 21 to Regulate Energy Balance and Remodeling of Adipose Tissue.

Objective: Restricting dietary methionine to 0.17% in mice increases energy expenditure (EE), reduces fat deposition, and improves metabolic health by increasing hepatic fibroblast growth factor 21 (FGF21). The goal of this study was to compare each of these responses in mice with the coreceptor for FGF21 deleted in either adipose tissue or the brain.

Sympathetic innervation of inguinal white adipose tissue in the mouse.

Adipose tissue plays an important role in metabolic homeostasis and its prominent role as endocrine organ is now well recognized. Adipose tissue is controlled via the sympathetic nervous system (SNS). New viral, molecular-genetic tools will soon allow a more detailed study of adipose tissue innervation in metabolic function, yet, the precise anatomical extent of preganglionic and postganglionic inputs to the inguinal white adipose tissue (iWAT) is limited.

Hepatic IKKε expression is dispensable for high-fat feeding-induced increases in liver lipid content and alterations in glucose tolerance.

There are endocrine and immunological changes that occur during onset and progression of the overweight and obese states. The inhibitor of nuclear factor-κB kinase-ε (IKKε) was originally described as an inducible protein kinase; whole body gene deletion or systemic pharmaceutical targeting of this kinase improved insulin sensitivity and glucose tolerance in mice. To investigate the primary sites of action associated with IKKε during weight gain, we describe the first mouse line with conditional elimination of IKKε in the liver (IKKε).

One week of continuous corticosterone exposure impairs hepatic metabolic flexibility, promotes islet β-cell proliferation, and reduces physical activity in male C57BL/6 J mice.

Clinical glucocorticoid use, and diseases that produce elevated circulating glucocorticoids, promote drastic changes in body composition and reduction in whole body insulin sensitivity. Because steroid-induced diabetes is the most common form of drug-induced hyperglycemia, we investigated mechanisms underlying the recognized phenotypes associated with glucocorticoid excess. Male C57BL/6 J mice were exposed to either 100ug/mL corticosterone (cort) or vehicle in their drinking water.

Response of Liver Metabolic Pathways to Ketogenic Diet and Exercise Are Not Additive.

Purpose: Studies suggest ketogenic diets (KD) produce favorable outcomes (health and exercise performance); however, most rodent studies have used a low-protein KD, which does not reflect the normal- to high-protein KD used by humans. Liver has an important role in ketoadaptation due to its involvement in gluconeogenesis and ketogenesis. This study was designed to test the hypothesis that exercise training (ExTr) while consuming a normal-protein KD (NPKD) would induce additive/synergistic responses in liver metabolic pathways.