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Two new diprenylated coumaric acid isomers (1a and 1b) and two known congeners, capillartemisin A (2) and B (3), were isolated from Artemisia scoparia as bioactive markers using bioactivity-guided HPLC fractionation. Their structures were determined by spectroscopic means, including 1D and 2D NMR methods and LC-MS, with their purity assessed by 1D 1H pure shift qNMR spectroscopic analysis. The bioactivity of compounds was evaluated by enhanced accumulation of lipids, as measured using Oil Red O staining, and by increased expression of several adipocyte marker genes, including adiponectin in 3T3-L1 adipocytes relative to untreated negative controls. Compared to the plant's 80% EtOH extract, these purified compounds showed significant but still weaker inhibition of TNFα-induced lipolysis in 3T3-L1 adipocytes. This suggests that additional bioactive substances are responsible for the multiple metabolically favorable effects on adipocytes observed with Artemisia scoparia extract.

To assess the metabolically beneficial effects of fenugreek (Trigonella foenum-graecum), C57BL/6J mice were fed a low- or high-fat diet for 16 weeks with or without 2% (w/w) fenugreek supplementation. Body weight, body composition, energy expenditure, food intake, and insulin/glucose tolerance were measured regularly, and tissues were collected for histological and biochemical analysis after 16 weeks of diet exposure. Fenugreek did not alter body weight, fat mass, or food intake in either group, but did transiently improve glucose tolerance in high fat-fed mice. Fenugreek also significantly improved high-density lipoprotein to low-density lipoprotein ratios in high fat-fed mice without affecting circulating total cholesterol, triglycerides, or glycerol levels. Fenugreek decreased hepatic expression of fatty acid-binding protein 4 and increased subcutaneous inguinal adipose tissue expression of adiponectin, but did not prevent hepatic steatosis. Notably, fenugreek was not as effective at improving glucose tolerance as was four days of voluntary wheel running. Overall, our results demonstrate that fenugreek promotes metabolic resiliency via significant and selected effects on glucose regulation, hyperlipidemia, and adipose pathology; but may not be as effective as behavioral modifications at preventing the adverse metabolic consequences of a high fat diet.

Adipocytes are important players in metabolic health and disease, and disruption of adipocyte development or function contributes to metabolic dysregulation. Hence, adipocytes are significant targets for therapeutic intervention in obesity and metabolic syndrome. Plants have long been sources for bioactive compounds and drugs. In previous studies, we screened botanical extracts for effects on adipogenesis in vitro and discovered that an ethanolic extract of Artemisia scoparia (SCO) could promote adipocyte differentiation. To follow up on these studies, we have used various separation methods to identify the compound(s) responsible for SCO's adipogenic properties. Fractions and subfractions of SCO were tested for effects on lipid accumulation and adipogenic gene expression in differentiating 3T3-L1 adipocytes. Fractions were also analyzed by Ultra Performance Liquid Chromatography- Mass Spectrometry (UPLC-MS), and resulting peaks were putatively identified through high resolution, high mass accuracy mass spectrometry, literature data, and available natural products databases. The inactive fractions contained mostly quercetin derivatives and chlorogenates, including chlorogenic acid and 3,5-dicaffeoylquinic acid, which had no effects on adipogenesis when tested individually, thus ruling them out as pro-adipogenic bioactives in SCO. Based on these studies we have putatively identified the principal constituents in SCO fractions and subfractions that promoted adipocyte development and fat cell gene expression as prenylated coumaric acids, coumarin monoterpene ethers, 6-demethoxycapillarisin and two polymethoxyflavones.

Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo.C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed.Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.

In addition to serving as a storage site for reserve energy, adipocytes play a critical role in whole-body insulin sensitivity and glucose metabolism. St. John’s Wort (SJW) is a botanical supplement widely used as an over-the-counter treatment of depression and a variety of other conditions associated with anxiety and nerve pain. Previous studies in our laboratory demonstrated that SJW inhibits insulin-stimulated glucose uptake and adipocyte differentiation in cultured murine and mature human adipocytes. To investigate the effects of SJW on adipocyte functionin vivo, we utilized C57BL/6J mice. In our studies, mice were administered SJW extract (200 mg/kg) once daily by gavage for two weeks. In contrast to ourin vitrostudies, mice treated with SJW extract showed increased levels of adiponectin in white adipose tissue in a depot specific manner(P<0.01). SJW also exerted an insulin-sensitizing effect as indicated by a significant increase in insulin-stimulated Akt serine phosphorylation in epididymal white adipose tissue(P<0.01). Food intake, body weight, fasting blood glucose, and fasting insulin did not differ between the two groups. These results are important as they indicate that SJW does not promote metabolic dysfunction in adipose tissuein vivo.

Adipose tissue development and function are widely studied to examine the relationship between obesity and the metabolic syndrome. It is well documented that the inability of adipose tissue to properly increase its lipid storage capacity during the obese state can lead to metabolic dysfunction. In a blind screen of 425 botanicals, we identified naringenin as an inhibitor of adipocyte differentiation. Naringenin is one of the most abundant citrus flavonoids, and recent studies have demonstrated antihyperlipidemic capabilities. These studies have largely focused on the effects of naringenin on the liver. Our biochemical studies clearly demonstrate that naringenin inhibits adipogenesis and impairs mature fat cell function. Naringenin specifically inhibited adipogenesis in a dose-dependent fashion as judged by examining lipid accumulation and induction of adipocyte marker protein expression. In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Exposure to naringenin also inhibited adiponectin protein expression in mature murine and human adipocytes. Our studies have revealed that naringenin may have a negative impact on adipocyte-related diseases by limiting differentiation of preadipocytes, by significantly inducing insulin resistance, and by decreasing adiponectin expression in mature fat cells.

Introduction Access to governmental and international nongovernmental sources of health care within eastern Myanmar's conflict regions is virtually nonexistent. Historically, under these circumstances effective care for the victims of trauma, particularly landmine injuries, has been severely deficient. Recognizing this, community-based organizations (CBOs) providing health care in these regions sought to scale up the capacity of indigenous health workers to provide trauma care. Case description The Trauma Management Program (TMP) was developed by CBOs in cooperation with a United States-based health care NGO. The goal of the TMP is to improve the capacity of local health workers to deliver effective trauma care. From 2000 to the present, international and local health care educators have conducted regular workshops to train indigenous health workers in the management of landmine injuries, penetrating and blunt trauma, shock, wound and infection care, and orthopedics. Health workers have been regularly resupplied with the surgical instruments, supplies and medications needed to provide the care learnt through TMP training workshops. Discussion and Evaluation Since 2000, approximately 300 health workers have received training through the TMP, as part of a CBO-run health system providing care for approximately 250 000 internally displaced persons (IDPs) and war-affected residents. Based on interviews with health workers, trauma registry inputs and photo/video documentation, protocols and procedures taught during training workshops have been implemented effectively in the field. Between June 2005 and June 2007, more than 200 patients were recorded in the trauma patient registry. The majority were victims of weapons-related trauma. Conclusion This report illustrates a method to increase the capacity of indigenous health workers to manage traumatic injuries. These health workers are able to provide trauma care for otherwise inaccessible populations in remote and conflicted regions. The principles learnt during the implementation of the TMP might be applied in similar settings.

Adipocytes play important roles in lipid storage, energy homeostasis and whole body insulin sensitivity. The JAK–STAT (Janus Kinase–Signal Transducer and Activator of Transcription) pathway mediates a variety of physiological processes including development, hematopoiesis, and inflammation. Although the JAK–STAT signaling pathway occurs in all cells, this pathway can mediate cell specific responses. Studies in the last two decades have identified hormones and cytokines that activate the JAK–STAT signaling pathway. These cytokines and hormones have profound effects on adipocytes. The content of this review will introduce the types of adipocytes and immune cells that make up adipose tissue, the impact of obesity on adipose cellular composition and function, and the general constituents of the JAK–STAT pathway and how its activators regulate adipose tissue development and physiology. A summary of the identification of STAT target genes in adipocytes reveals how these transcription factors impact various areas of adipocyte metabolism including insulin action, modulation of lipid stores, and glucose homeostasis. Lastly, we will evaluate exciting new data linking the JAK–STAT pathway and brown adipose tissue and consider the future outlook in this area of investigation. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

A large, negative DeltaCp of DNA binding is a thermodynamic property of the majority of sequence-specific DNA-protein interactions, and a common, but not universal property of non-sequence-specific DNA binding. In a recent study of the binding of Taq polymerase to DNA, we showed that both the full-length polymerase and its "Klentaq" large fragment bind to primed-template DNA with significant negative heat capacities. Herein, we have extended this analysis by analyzing this data for temperature-variable heat capacity effects (DeltaDeltaCp), and have similarly analyzed an additional 47 protein-DNA binding pairs from the scientific literature. Over half of the systems examined can be easily fit to a function that includes a DeltaDeltaCp parameter. Of these, 90% display negative DeltaDeltaCp values, with the result that the DeltaCp of DNA binding will become more negative with rising temperature. The results of this collective analysis have potentially significant consequences for current quantitative theories relating DeltaCp values to changes in accessible surface area, which rely on the assumption of temperature invariance of the DeltaCp of binding. Solution structural data for Klentaq polymerase demonstrate that the observed heat capacity effects are not the result of a coupled folding event.