A Combined Transcriptomics and Lipidomics Analysis of Subcutaneous, Epididymal and Mesenteric Adipose Tissue Reveals Marked Functional Differences

Depot-dependent differences in adipose tissue physiology may reflect specialized functions and local interactions between adipocytes and surrounding tissues. We combined time-resolved microarray analyses of mesenteric- (MWAT), subcutaneous- (SWAT) and epididymal adipose tissue (EWAT) during high-fat feeding of male transgenic ApoE3Leiden mice with histology, targeted lipidomics and biochemical analyses of metabolic pathways to identify differentially regulated processes and site-specific functions. EWAT was found to exhibit physiological zonation. De novo lipogenesis in fat proximal to epididymis was stably low, whereas de novo lipogenesis distal to epididymis and at other locations was down-regulated in response to high-fat diet. The contents of linoleic acid and α-linolenic acid in EWAT were increased compared to other depots. Expression of the androgen receptor (Ar) was higher in EWAT than in MWAT and SWAT. We suggest that Ar may mediate depot-dependent differences in de novo lipogenesis rate and propose that accumulation of linoleic acid and α-linolenic acid in EWAT is favored by testosterone-mediated inhibition of de novo lipogenesis and may promote further elongation and desaturation of these polyunsaturated fatty acids during spermatogenesis

The Anti-Inflammatory and Antibacterial Basis of Human Omental Defense: Selective Expression of Cytokines and Antimicrobial Peptides

BACKGROUND: The wound healing properties of the human omentum are well known and have extensively been exploited clinically. However, the underlying mechanisms of these effects are not well understood. We hypothesize that the omentum tissue promotes wound healing via modulation of anti-inflammatory pathways, and because the omentum is rich in adipocytes, the adipocytes may modulate the anti-inflammatory response. Factors released by human omentum may affect healing, inflammation and immune defense. METHODOLOGY: Six human omentum tissues (non obese, free from malignancy, and any other systemic disorder) were obtained during diagnostic laparoscopies having a negative outcome. Healthy oral mucosa (obtained from routine oral biopsies) was used as control. Cultured adipocytes derived from human omentum were exposed to lipopolysaccharide (LPS) (1-50 ng/mL) for 12-72 hours to identify the non-cytotoxic doses. Levels of expression (mRNA and protein) were carried out for genes associated with pro- and anti-inflammatory cytokine responses and antibacterial/antimicrobial activity using qRT-PCR, western blotting, and cell-based ELISA assays. RESULTS: The study shows significant higher levels of expression (mRNA and protein) of several specific cytokines, and antibacterial peptides in the omentum tissues when compared to oral sub-mucosal tissues. In the validation studies, primary cultures of adipocytes, derived from human omentum were exposed to LPS (5 and 10 ng/mL) for 24 and 48 h. The altered expressions were more pronounced in cultured adipocytes cells when exposed to LPS as compared to the omentum tissue. CONCLUSIONS/SIGNIFICANCE: Perhaps, this is the first report that provides evidence of expressional changes in pro- and anti-inflammatory cytokines and antibacterial peptides in the normal human omentum tissue as well as adipocytes cultured from this tissue. The study provides new insights on the molecular and cellular mechanisms of healing and defense by the omentum, and suggests the potential applicability of cultured adipocytes derived from the omentum for future therapeutic applications

Changes in adipocytes and dendritic cells in lymph node-containing adipose depots during and after many weeks of mild inflammation

The time course and cellular basis for inflammation-induced hypertrophy of adipose tissue were investigated over 20 weeks in mature male rats. Mild inflammation was induced by subcutaneous injection of 20 µg lipopolysaccharide into one hind-leg three times/week for 4 or 8 weeks, followed by up to 12 weeks ‘rest’ without intervention. Mean volume and frequency of apoptosis (TUNEL assay) were measured in adipocytes isolated from sites defined by their anatomical relations to lymph nodes, plus numbers of C6kine-stimulated lymph node-derived and adipose tissue-derived dendritic cells. Experimental inflammation increased dendritic cells and adipocyte apoptosis in the locally-stimulated popliteal depot and the lymphoid tissue-associated regions of the contralateral popliteal and mesentery and omentum. Responses declined slowly after inflammation ended, but all measurements from the locally-stimulated popliteal depot, and the omentum, were still significantly different from controls after 12 weeks rest. The locally-stimulated popliteal adipose tissue enlarged by 5% within 4 weeks and remained larger than the control. We conclude that prolonged inflammation induces permanent enlargement, greater adipocyte turnover and increased dendritic cell surveillence in the adjacent adipose tissue and the omentum. The experiment suggests a mechanism for selective hypertrophy of lymphatics-associated adipose tissue in chronic stress and inflammatory disorders including impaired lymph drainage, Crohn’s disease and HIV-associated lipodystrophy, and a link between evolutionary fitness, sexual selection and aesthetically pleasing body symmetry. It would be useful for further study of molecular mechanisms in inflammation-induced local hypertrophy of adipose tissue and development of specific therapies that avoid interference with whole-body lipid metabolism

Site-specific differences in fatty acid composition of dendritic cells and associated adipose tissue in Popliteal Depot, Mesentery, and Omentum and their modulation by chronic inflammation and dietary lipids

Background: This study explores the role of lymphatics-associated adipocytes in determining the lipid composition of dendritic cells. Methods and Results: Adult male rats were fed plain chow, or chow supplemented with 20% sunflower or fish oil. Chronic local inflammation was induced by subcutaneous injection of 20 µg lipopolysaccharide three times a week for 2 weeks near the popliteal lymph nodes. Chemokine-stimulated dendritic cells were collected over 4 h from popliteal and mesenteric lymph nodes, and perinodal and other samples of mesenteric, popliteal and omental adipose tissue. Fatty acids extracted from triacylglycerols and/or phospholipids were separated and quantified by gas chromatography from each sample of dendritic cells and intracellular lipids, membranes, stroma and isolated adipocytes from the adipose tissue. Dendritic cells from lymph nodes and adipose tissue samples differ in fatty acid composition, and can be modulated by diet. The site-specific differences of dendritic cells correlate with those of the contiguous adipocytes. Chronic mild stimulation alters the lipid composition of dendritic cells near the inflamed site and elsewhere; changes are minimal after the fish-oil diet. The composition of adipocyte triacylglycerol and phospholipid fatty acids also changes near the stimulation site in ways that counteract alterations induced by the experimental diets. Conclusions: Fatty acids in dendritic cells differ with anatomical site, and are determined by the adjacent adipocytes, which actively regulate their own lipid composition. These findings demonstrate functional bases for the anatomical associations between adipose and lymphoid tissues and may be a mechanism by which dietary lipids modulate the immune system

Elementi di chimica del suolo

Il suolo non \ue8 solo il substrato sul quale poggiano i nostri piedi ma \ue8 anche la sede di tutto un mondo, dalle piante agli animali, ai microrganismi che vi trovano nutrimento, ambiente accogliente, in poche parole condizioni di vita. Inoltre essendo a contatto diretto con l\u2019atmosfera, reagisce e interagisce con essa in una serie di processi fisici e chimici capaci di modificarlo profondamente. Il suolo \ue8 un essere vivente e come tale soggiace a cambiamenti che, in armonia con le leggi naturali della fisica, della chimica e della biologia, e sotto la costante pressione antropica, lo indirizzano in una evoluzione inesorabile ed in alcuni casi irreversibile. Una caratteristica che salta agli occhi \ue8 la sua estrema variabilit\ue0, di aspetto, di composizione, di propriet\ue0. La chimica del suolo \ue8 una scienza che studia i suoli nei riguardi i) della loro composizione, ii) dei processi fisici, chimici e biologici che li hanno originati e iii) della loro reagibilit\ue0 di fronte a qualsiasi agente chimico naturale od artificiale. Lo studio della dinamica chimica a cui il suolo continuamente soggiace \ue8 alla base della comprensione delle sue capacit\ue0 a sostenere e nutrire le piante di interesse agrario e forestale, nonch\ue9 la vita umana