Ghrelin and the differential regulation of des-acyl (DSG) and oct-anoyl ghrelin (OTG) in human adipose tissue (AT)

Objectives Ghrelin, an important central acting orexigenic hormone, is predominantly secreted in the gastrointestinal tract. However little is known about the action of ghrelin in human adipose tissue (AT). Aim To study the expression of ghrelin in AT, the effects of octanoyl–(OTG) and des-acyl (DSG) ghrelin on lipolysis and lipogenesis, leptin release and potential peripheral signalling through the Y1 receptor. Methods Ex vivo human AT was obtained from women undergoing elective surgery (46 (mean ± SD) 6·8 years, body mass index (BMI): 25·6 ± 5·0 kg/m2, n = 20). Abdominal-subcutaneous (AbdSc) adipocytes were isolated and treated with recombinant human (rh) OTG and DSG to assess lipid metabolism leptin release and the influence of Y1-receptor blocker. Results Ghrelin was expressed in AbdScAT and negatively correlated with BMI (lean: 3·6 ± 0·74 optical-density-units (OD), obese: 1·64 ± 0·45OD, *P < 0·05). Only DSG significantly suppressed glycerol release (Control (C): 286 ± 58 µl/l; DSG 1 nm: 224 ± 38 µl/l↓*; DSG 100 nm: 172 ± 13 µl/l↓*,*↓P < 0·05, n = 7) and reduced hormone sensitive lipase expression (C: 1·0 ± 0·3OD; DSG 1 nm: 0·8 ± 0·3OD↓*; DSG 100 nm: 0·6 ± 0·1OD↓*, n = 4). However, both isoforms increased lipoprotein lipase expression (C: 1·0 ± 0·3OD; DSG 100 nm: 0·2 ± 0·4OD↑*; OTG 100 nm: 2·5 ± 0·3OD↑*, n = 4), whilst blockade of Y1 eliminated this effect in both. Leptin was down-regulated by DSG only (DSG 1 nm: 5·3 ± 0·7 ng/ml; DSG 100 nm: 4·1 ± 0·7 ng/ml*) and was significant after BMI adjustment (P = 0·029). Conclusion Ghrelin was expressed in human AbdSc AT. In vitro, both OGT and DSG appear to mediate fat deposition with the lipogenic effects in part mediated by the Y1 receptor, whilst the influence of DSG affected lipolysis, lipogenesis and leptin secretion. Taken together, these studies support a local action for ghrelin isoforms on lipid and adipokine metabolism that further supports a cross talk between organs