Creeping Fat-Derived Free Fatty Acids Induce Hyperplasia of Intestinal Muscularis Propria Muscle Cells: A Novel Link Between Fat and Intestinal Stricture Formation in Crohn's Disease.

Background & Aims: In Crohn's disease, wrapping of mesenteric fat around the bowel wall, so-called "creeping fat," is highly associated with strictures. The strongest contributor to luminal narrowing in strictures is a thickening of the human intestinal muscularis propria (MP). We investigated creeping fat-derived factors and their effect on mechanisms of human intestinal MP smooth muscle cell (HIMC) hyperplasia.

Adipose tissue fibrosis: the unwanted houseguest invited by obesity.

The prevalence of obesity is increasing exponentially across the globe. The lack of effective treatment options for long-term weight loss has magnified the enormity of this problem. Studies continue to demonstrate that adipose tissue holds a biological memory, one of the most important determinant of long-term weight maintenance.

Adipose tissue macrophages exert systemic metabolic control by manipulating local iron concentrations.

Iron is essential to many fundamental biological processes, but its cellular compartmentalization and concentration must be tightly controlled. Although iron overload can contribute to obesity-associated metabolic deterioration, the subcellular localization and accumulation of iron in adipose tissue macrophages is largely unknown. Here, we show that macrophage mitochondrial iron levels control systemic metabolism in male mice by altering adipocyte iron concentrations.

Adipocyte mesenchymal transition contributes to mammary tumor progression.

Obesity is associated with increased cancer incidence and progression. However, the relationship between adiposity and cancer remains poorly understood at the mechanistic level. Here, we report that adipocytes from tumor-invasive mammary fat undergo de-differentiation to fibroblast-like precursor cells during tumor progression and integrate into the tumor microenvironment.

A new signal that shrinks fat.

Healthy white adipose tissue is dependent on proliferation of endothelial cells to maintain homeostasis or undergo expansion. A new study shows that endothelial cells communicate with adipocytes via polyamines to promote vascularization of adipose tissue, thereby reversing the metabolic effects of obesity.

Gut microbe-targeted choline trimethylamine lyase inhibition improves obesity via rewiring of host circadian rhythms.

Obesity has repeatedly been linked to reorganization of the gut microbiome, yet to this point obesity therapeutics have been targeted exclusively toward the human host. Here, we show that gut microbe-targeted inhibition of the trimethylamine N-oxide (TMAO) pathway protects mice against the metabolic disturbances associated with diet-induced obesity (DIO) or leptin deficiency (). Small molecule inhibition of the gut microbial enzyme choline TMA-lyase (CutC) does not reduce food intake but is instead associated with alterations in the gut microbiome, improvement in glucose tolerance, and enhanced energy expenditure.

Extracellular vesicle-based interorgan transport of mitochondria from energetically stressed adipocytes.

Adipocytes undergo intense energetic stress in obesity resulting in loss of mitochondrial mass and function. We have found that adipocytes respond to mitochondrial stress by rapidly and robustly releasing small extracellular vesicles (sEVs). These sEVs contain respiration-competent, but oxidatively damaged mitochondrial particles, which enter circulation and are taken up by cardiomyocytes, where they trigger a burst of ROS.

Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis.

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism.

Adiponectin preserves metabolic fitness during aging.

Adiponectin is essential for the regulation of tissue substrate utilization and systemic insulin sensitivity. Clinical studies have suggested a positive association of circulating adiponectin with healthspan and lifespan. However, the direct effects of adiponectin on promoting healthspan and lifespan remain unexplored.

Mitochondrial metabolism is a key regulator of the fibro-inflammatory and adipogenic stromal subpopulations in white adipose tissue.

The adipose tissue stroma is a rich source of molecularly distinct stem and progenitor cell populations with diverse functions in metabolic regulation, adipogenesis, and inflammation. The ontology of these populations and the mechanisms that govern their behaviors in response to stimuli, such as overfeeding, however, are unclear. Here, we show that the developmental fates and functional properties of adipose platelet-derived growth factor receptor beta (PDGFRβ)+ progenitor subpopulations are tightly regulated by mitochondrial metabolism.

Dermal adipocytes contribute to the metabolic regulation of dermal fibroblasts.

Dermal fibroblasts are an essential population of skin cells. They are not only responsible for synthesis and remodelling of the extracellular matrix of the dermis, but also communicate with other skin cells via autocrine and paracrine interactions. Skin-associated dermal adipocytes reside below the reticular dermis.

Critical lipids link breastfeeding to healthy adipose tissue in infancy and adulthood.

The study of beige adipose tissue (BeAT) has recently gained popularity because of its potential as a therapeutic target for the treatment of obesity and other metabolic disorders. While BeAT regulation is well understood in adults, the critical signals regulating BeAT during infant development need to be better defined. The bioactive components in breast milk have been primarily studied in the context of immunity.

The retinol-binding protein receptor STRA6 regulates diurnal insulin responses.

It has long been appreciated that insulin action is closely tied to circadian rhythms. However, the mechanisms that dictate diurnal insulin sensitivity in metabolic tissues are not well understood. Retinol-binding protein 4 (RBP4) has been implicated as a driver of insulin resistance in rodents and humans, and it has become an attractive drug target in type II diabetes.

The contribution of endogenous and exogenous factors to male alopecia: a study of identical twins.

Background: The purpose of this study was to investigate the potential contribution of environmental factors and testosterone on male alopecia.

Methods: Ninety-two identical male twins were recruited from 2009 to 2011. A comprehensive questionnaire was completed followed by the acquisition of sputum samples for testosterone analysis and standardized digital photography.

The role of different methods of nerve ablation in prevention of neuroma.

Background: The aim of this study was to compare the incidence of neuroma formation and neuropathic pain following different techniques of nerve ablation in a rat sural nerve model.

Methods: Rat sural nerve was subjected to four different techniques of ablation with standardized creation of a 1-cm gap (n = 15 in each group). These included nerve avulsion, transection and burying in muscle, transection and folding of nerve, and transection alone.

The contribution of endogenous and exogenous factors to female alopecia: a study of identical twins.

Background: In this study, the authors investigated the potential contribution of environmental factors and testosterone levels on androgenic alopecia in women.

Methods: Ninety-eight identical female twins were recruited from 2009 to 2011. Subjects were asked to complete a comprehensive questionnaire, provide a sputum sample for testosterone analysis, and pose for standardized digital photography.

Stromal-cell-derived factor (SDF) 1-alpha in combination with BMP-2 and TGF-β1 induces site-directed cell homing and osteogenic and chondrogenic differentiation for tissue engineering without the requirement for cell seeding.

The clinical translation of tissue engineering approaches is limited by the requirement of a cell source. Cell guidance is a new concept that provides an alternative approach, obviating a requirement for an external cell source. This relies on site-specific homing and differentiation of the patient's own cells to an implanted scaffold through controlled delivery of cytokines.

Propranolol induces regression of hemangioma cells through HIF-1α-mediated inhibition of VEGF-A.

Objective: To investigate the mechanism of propranolol on regression of infantile hemangiomas.

Background: Propranolol has been found to be effective in treatment of severe hemangiomas of infancy. However, its mechanism of action is as yet unknown.

TGF-beta1 RNA interference in mouse primary dura cell culture: downstream effects on TGF receptors, FGF-2, and FGF-R1 mRNA levels.

Background: Transforming growth factor (TGF)-beta1 and fibroblast growth factor (FGF)-2 have both been shown to have significant roles in the regulation of murine calvarial suture fusion. Methods to decrease gene expression of these cytokines and their respective receptors have been established, but because of side effects, clinical applications are limited. In this study, the authors examined the effect of TGF-beta1-specific small interfering RNA (siRNA) on the messenger RNA (mRNA) expression of TGF-beta1, its TGF-betaR1 and TGF-betaR2 receptors, and FGF-2 and its R1 receptor in murine dura cells.

Nonviral transfection of mouse calvarial organ in vitro using Accell-modified siRNA.

Background: Understanding the biology of cranial suture fusion and the precise role of involved molecules implicated in the process will help to identify key factors involved in regulation of suture fusion. Modulation of these key factors may serve as a tissue-engineering technique to replace the traditional surgical procedures for the correction of premature suture fusion. Modulation of gene expression by RNA interference is a widely used technique with high potential.

Serum metabolite profiles and target tissue gene expression define the effect of cholecalciferol intake on calcium metabolism in rats and mice.

We studied the effect of cholecalciferol (VD3) intake on VD3 status and markers of calcium (Ca) homeostasis in mice and rats. Serum 25 hydroxycholecalciferol (25OH-VD3) concentrations were increased in animals fed diets containing 400-20,000 international units (IU) VD3/kg (37 nmol.L(-1).

High dietary vitamin D prevents hypocalcemia and osteomalacia in CYP27B1 knockout mice.

Mice lacking 25-hydroxycholecalciferol [25(OH)D]-1alpha-hydroxylase (CYP27B1) are growth retarded, hypocalcemic, and have poor bone mineralization. We tested whether high dietary cholecalciferol (VD3) could exert effects in the absence of CYP27B1 in vivo. Weanling male wild-type (WT) and CYP27B1 knockout (KO) mice were fed either a 2% calcium (Ca), 20% lactose rescue diet or an AIN93G diet (0.