The source of fatty acids incorporated into proliferating lymphoid cells in immune-stimulated lymph nodes

To explore the hypothesis that proliferating lymphoid cells in immune-stimulated lymph nodes obtain nutrients locally from adjacent adipose tissue, adult guinea-pigs were fed for six weeks on standard chow or on chow supplemented with 10% suet, sunflower oil or fish oil. All ate standard chow for the last five days, during which swelling of one popliteal lymph node was stimulated by repeated local injection of lipopolysaccharide. The fatty acid compositions of phospholipids in both popliteal and in several mesenteric lymph nodes, and of triacylglycerols in 11 samples of adipose tissue defined by their anatomical relations to lymph nodes, were determined by gas chromatography. The proportions of fatty acids in the phospholipids extracted from the stimulated popliteal node correlated best with those of triacylglycerols in the surrounding adipocytes, less strongly with those of adipocytes elsewhere in depots associated with lymphoid tissue, but not with those of nodeless depots. The composition of triacylglycerols in the perinodal adipose tissue may change under local immune stimulation. We conclude that proliferating lymphoid cells in activated lymph nodes obtain fatty acids mainly from the triacylglycerols in adjacent perinodal adipose tissue. Immune stimulation prompts changes in the fatty acid composition of the triacylglycerols of adipocytes in node-containing depots that equip the adipose tissue for provisioning immune responses. Such local interactions show that specialised adipocytes can act as an interface between whole-body and cellular nutrition, and may explain why mammalian adipose tissue is partitioned into a few large and many small depots

Investigating interactions between epicardial adipose tissue and cardiac myocytes: what can we learn from different approaches?

Heart disease is a major cause of morbidity and mortality throughout the world. Some cardiovascular conditions can be modulated by lifestyle factors such as increased exercise or a healthier diet, but many require surgical or pharmacological interventions for their management. More targeted and less invasive therapies would be beneficial. Recently it has become apparent that epicardial adipose tissue plays an important role in normal and pathological cardiac function, and it is now the focus of considerable research. Epicardial adipose tissue can be studied by imaging of various kinds, and these approaches have yielded much useful information. However at a molecular level it is more difficult to study as it is relatively scarce in animal models and, for practical and ethical reasons, not always available in sufficient quantities from patients. What is needed is a robust model system in which the interactions between epicardial adipocytes and cardiac myocytes can be studied, and physiologically relevant manipulations performed. There are drawbacks to conventional culture methods, not least the difficulty of culturing both cardiac myocytes and adipocytes, each of which has special requirements. We discuss the benefits of a three-dimensional co-culture model in which in vivo interactions can be replicated

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

Visceral adipose tissue immune homeostasis is regulated by the crosstalk between adipocytes and dendritic cell subsets

Visceral adipose tissue (VAT) has multiple roles in orchestrating whole-body energy homeostasis. In addition, VAT is now considered an immune site harboring an array of innate and adaptive immune cells with a direct role in immune surveillance and host defense. We report that conventional dendritic cells (cDCs) in VAT acquire a tolerogenic phenotype through upregulation of pathways involved in adipocyte differentiation. While activation of the Wnt/β-catenin pathway in cDC1 DCs induces IL-10 production, upregulation of the PPARγ pathway in cDC2 DCs directly suppresses their activation. Combined, they promote an anti-inflammatory milieu in vivo delaying the onset of obesity-induced chronic inflammation and insulin resistance. Under long-term over-nutrition, changes in adipocyte biology curtail β-catenin and PPARγ activation, contributing to VAT inflammation

Regulatory bodies: Dramatic creativity, control and the commodity of Lady Audley's Secret

This article investigates how the playwrights of the Victorian era creatively exploited the loopholes in copyright and licensing laws. I argue that in depicting the heroine Lady Audley's bodily display, they themselves engage with the issues of regulatory control and freedom