Opipramol inhibits lipolysis in human adipocytes without altering glucose uptake and differently from antipsychotic and antidepressant drugs with adverse effects on body weight control

Treatment with several antipsychotic drugs exhibits a tendency to induce weight gain and diabetic complications. The proposed mechanisms by which the atypical antipsychotic drug olanzapine increases body weight include central dysregulations leading to hyperphagia and direct peripheral impairment of fat cell lipolysis. Several investigations have reproduced in vitro direct actions of antipsychotics on rodent adipocytes, cultured preadipocytes, or human adipose tissue-derived stem cells. However, to our knowledge, no such direct action has been described in human mature adipocytes. The aim of the present study was to compare in human adipocytes the putative direct alterations of lipolysis by antipsychotics (haloperidol, olanzapine, ziprazidone, risperidone), antidepressants (pargyline, phenelzine), or anxiolytics (opipramol). Lipolytic responses to the tested drugs, and to recognized lipolytic (e.g., isoprenaline) or antilipolytic agents (e.g., insulin) were determined, together with glucose transport and amine oxidase activities in abdominal subcutaneous adipocytes from individuals undergoing plastic surgery. None of the tested drugs were lipolytic. Surprisingly, only opipramol exhibited substantial antilipolytic properties in the micromolar to millimolar range. An opipramol antilipolytic effect was evident against isoprenaline-, forskolin-, or atrial natriuretic peptide-stimulated lipolysis. Opipramol did not impair insulin activation of glucose transport but inhibited monoamine oxidase (MAO) activity to the same extent as antidepressants recognized as MAO inhibitors (pargyline, harmine, or phenelzine), whereas antipsychotics were inefficient. Considering its unique properties, opipramol, which is not associated with weight gain in treated patients, is a good candidate for drug repurposing because it limits exaggerated lipolysis, prevents hydrogen peroxide release by amine oxidases in adipocytes, and is thereby of potential use to limit lipotoxicity and oxidative stress, two deleterious complications of diabetes and obesity

The role of the land-surface model for climate change projections over the Iberian Peninsula

The importance of land-surface processes within Regional Climate Models for accurately reproducing the present-day climate is well known. However, their role when projecting future climate is still poorly reported. Hence, this work assesses the influence of the land-surface processes, particularly the contribution of soil moisture, when projecting future changes for temperature, precipitation and wind over a complex area as the Iberian Peninsula, which, in addition, shows great sensitivity to climate change. The main signals are found for the summer season, when the results indicate a strengthening in the increases projected for both mean temperature and temperature variability as a consequence of the future intensification of the positive soil moisture-temperature feedback. The more severe warming over the inner dry Iberian Peninsula further implies an intensification of the Iberian thermal low and, thus, of the cyclonic circulation. Furthermore, the land-atmosphere coupling leads to the projection of a wider future daily temperature range, since maximum temperatures are more affected than minima, a feature absent in non-coupled simulations. Regarding variability, the areas where the land-atmosphere coupling introduces larger changes are those where the reduction in the soil moisture content is more dramatic in future simulations, i.e., the so-called transitional zones. As regards precipitation, weaker positive signals for convective precipitation and more intense negative signals for non-convective precipitation are obtained as a result of the soil moisture-atmosphere interactions. These results highlight the crucial contribution of soil moisture to climate change projections and suggest its plausible key role for future projections of extreme events

Formulations of Plant Growth-Promoting Microbes for Field Applications

Development of a plant growth-promoting (PGP) microbe needs several steps starting with isolation of a pure culture, screening of its PGP or antagonistic traits by means of different efficacy bioassays performed in vitro, in vivo or in trials under greenhouse and/or field conditions. In order to maximize the potential of an efficient PGP microbe, it is essential to optimize mass multiplication protocols that promote product quality and quantity and a product formulation that enhances bioactivity, preserves shelf life and aids product delivery. Selection of formulation is very crucial as it can determine the success or failure of a PGP microbe. A good carrier material should be able to deliver the right number of viable cells in good physiological conditions, easy to use and economically affordable by the farmers. Several carrier materials have been used in formulation that include peat, talc, charcoal, cellulose powder, farm yard manure, vermicompost and compost, lignite, bagasse and press mud. Each formulation has its advantages and disadvantages but the peat based carrier material is widely used in different part of the world. This chapter gives a comprehensive analysis of different formulations and the quality of inoculants available in the market, with a case study conducted in five-states of India

Murine in vitro cellular models to better understand adipogenesis and its potential applications

Adipogenesis has been extensively studied using in vitro models of cellular differentiation, enabling long-term regulation of fat cell metabolism in human adipose tissue (AT) material. Many studies promote the idea that manipulation of this process could potentially reduce the prevalence of obesity and its related diseases. It has now become essential to understand the molecular basis of fat cell development to tackle this pandemic disease, by identifying therapeutic targets and new biomarkers. This review explores murine cell models and their applications for study of the adipogenic differentiation process in vitro. We focus on the benefits and limitations of different cell line models to aid in interpreting data and selecting a good cell line model for successful understanding of adipose biology

Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1

OBJECTIVE: Development of brown-like/beige adipocytes in white adipose tissue (WAT) helps to reduce obesity. Thus, we investigated the effects of resveratrol, a dietary polyphenol capable of preventing obesity and related complications in humans and animal models, on brown-like adipocyte formation in inguinal WAT (iWAT). METHODS: CD1 female mice (5-month-old) were fed a high-fat diet with/without 0.1% resveratrol. In addition, primary stromal vascular cells separated from iWAT were subjected to resveratrol treatment. Markers of brown-like (beige) adipogenesis were measured and the involvement of AMP-activated protein kinase (AMPK) α1 was assessed using conditional knockout. RESULTS: Resveratrol significantly increased mRNA and/or protein expression of brown adipocyte markers including uncoupling protein 1 (UCP1), PR domain-containing 16 (PRDM16), Cell death-inducing DFFA-like effector A (Cidea), elongation of very long chain fatty acids protein 3 (Elovl3), peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), cytochrome C and pyruvate dehydrogenase (PDH) in differentiated iWAT stromal vascular cells (SVC), suggesting that resveratrol induced brown-like adipocyte formation in vitro. Concomitantly, resveratrol markedly enhanced AMPKα1 phosphorylation and differentiated SVC oxygen consumption. Such changes were absent in cells lacking AMPKα1, showing that AMPKα1 is a critical mediator of resveratrol action. Resveratrol also induced beige adipogenesis in vivo along with the appearance of multiocular adipocytes, increased UCP1 expression and enhanced fatty acid oxidation. CONCLUSION: Resveratrol induces brown-like adipocyte formation in iWAT via AMPKα1 activation and suggest that its beneficial anti-obesity effects may be partly due to the browning of WAT and as a consequence, increased oxygen consumption