Adipokines and the role of visceral adipose tissue in inflammatory bowel disease.

Recently, adipocytes have been recognized as actively participating in local and systemic immune responses via the secretion of peptides detectable in relevant levels in the systemic circulation, the so-called "adipo(cyto)kines". Multiple studies appearing within the last 10-15 years have focused on the possible impact of adipose tissue depots on inflammatory bowel disease (IBD). Consequently, various hypotheses regarding the role of different adipokines in inflammatory diseases in general and in intestinal inflammatory processes in particular have been developed and have been further refined in recent years. After a focused summary of the data reported concerning the impact of visceral adipose tissue on IBD, such as Crohn's disease and ulcerative colitis, our review focuses on recent developments indicating that adipocytes as part of the innate immune system actively participate in antimicrobial host defenses in the context of intestinal bacterial translocation, which are of utmost importance for the homeostasis of the whole organism. Modulators of adipose tissue function and regulators of adipokine secretion, as well as modifiers of adipocytic pattern recognition molecules, might represent future potential drug targets in IBD.

Living-donor parathyroid allotransplantation for therapy-refractory postsurgical persistent hypoparathyroidism in a nontransplant recipient - three year results: a case report.

BACKGROUND: Therapy-refractory persistent hypoparathyroidism after extensive neck surgery is a rare but severe complication. Parathyroid allotransplantation may represent a definitive treatment option. CASE PRESENTATION: A 32-year old female was referred to our hospital with intractable persistent hypocalcemia after neck surgery for papillary thyroid cancer. Despite optimal medical treatment including calcium and vitamin D supplementation and even hormonal replacement therapy hypocalcemic symptoms failed to improve. The quality of life was considered very low. In light of the unsuccessful medical therapy and the young age of the patient parathyroid allotransplantation seemed an attractive treatment option to restore normal calcium homeostasis despite of the need for immunosuppressive therapy after the procedure. Therefore, we performed living-donor allotransplantation of two healthy parathyroid glands to the recipient's left forearm. The surgical intervention was successful. Neither the donor nor the recipient showed any complications. In the postoperative course clinical symptoms of hypocalcemia significantly improved whereas serum calcium and parathyroid hormone (PTH) levels progressively increased into the normal range. Former intense replacement therapy could be discontinued completely in a stepwise fashion. To date, nearly three years after transplantation, the patient remains asymptomatic with normal serum levels of calcium and PTH. CONCLUSION: Successful living-donor parathyroid allotransplantation for postsurgical hypoparathyroidism represents an innovative therapeutic strategy that could provide the definitive treatment in those patients in which the disease is therapy-refractory. The procedure can be justified even in nontransplant recipients. Retrieval of parathyroid glands from healthy donors is feasible and safe.

Fatty acid-induced induction of Toll-like receptor-4/nuclear factor-kappaB pathway in adipocytes links nutritional signalling with innate immunity.

To study the effects of fatty acids and the involvement of the Toll-like receptor-4/nuclear factor-kappaB (TLR-4/NF-kappaB) pathway with respect to the secretion of adipokines from adipocytes 3T3-L1 adipocytes were stimulated with increasing doses of fatty acids. The secretion of adiponectin, resistin and monocyte chemoattractant protein-1 (MCP-1) was measured by enzyme-linked immunosorbent assay. The NF-kappaB p65 nuclear translocation and TLR-4 expression were investigated by Western blot. The effects mediated by NF-kappaB were tested using a specific NF-kappaB-inhibitor and TLR-4-induced effects were analysed with a neutralizing TLR-4 antibody. Binding of (14)C-labelled fatty acids to TLR-4/MD-2 was investigated using a FLAG-tagged extracellular part of TLR-4 fused to full-length MD-2 via a linker (lipopolysaccharide-Trap). The messenger RNA (mRNA) expression of adipokines in abdominal adipose tissue of rats fed a standard chow or a high-fat diet was investigated by reverse transcription-polymerase chain reaction. The TLR-4 is induced during adipocyte differentiation and its expression is enhanced following fatty acid stimulation. The stimulatory effects of stearic and palmitic acids on MCP-1 secretion and of palmitoleic acid on resistin secretion are mediated via NF-kappaB. The stimulatory effects of stearic, palmitic and palmitoleic acids on resistin secretion and the stimulatory effect of stearic acid on MCP-1 secretion are mediated via TLR-4. Fatty acid-mediated effects are caused by an endogenous ligand because fatty acids were shown not to bind directly to TLR-4/MD-2. Adipose tissue mRNA expression and serum levels of adipokines did not differ in rats fed a high-fat diet. These data provide a new molecular mechanism by which fatty acids can link nutrition with innate immunity.

High molecular weight adiponectin reduces apolipoprotein B and E release in human hepatocytes.

Low circulating levels of high molecular weight adiponectin (HMW-Apm) have been linked to dyslipidaemia and systemic HMW-Apm negatively correlates with very low density lipoprotein (VLDL), apolipoprotein B (ApoB), and ApoE and is positively associated with ApoA-I. Therefore, it was investigated whether HMW-Apm alters the hepatic synthesis of ApoB, ApoE, and ApoA-I or the activity of the hepatic ATP-binding cassette transporter A1 (ABCA1), as the main determinant of plasma HDL. HMW-Apm reduces hepatic ApoB and ApoE release whereas ABCA1 protein, activity and ApoA-I were not altered. Global gene expression analysis revealed that hepatic nuclear factor 4-alpha (HNF4-alpha) and HNF4-alpha regulated genes like ApoB are downregulated by HMW-Apm and this was confirmed at the mRNA and protein level. Therefore it is concluded that HMW-adiponectin may ameliorate dyslipidaemia by reducing the hepatic release of ApoB and ApoE, whereas ABCA1 function and ApoA-I secretion are not influenced.