Serum antibodies against major outer membrane protein (MOMP) and heat shock protein 60 (HSP60) from Chlamydia trachomatis are correlated with sequelae following infection. Since bacterial and human HSP60 share considerable sequence homology, cross-reactivity to human HSP60 is suggested as being involved in tubal factor infertility (TFI). The aim was to investigate whether antibodies to human HSP60 are associated with TFI, and to evaluate antibody testing in TFI diagnosis. Serum levels of antibodies against chlamydial MOMP and HSP60 from C. trachomatis, Salmonella enterica Enteritidis, Campylobacter jejuni and human HSP60 were analysed by enzyme-linked immunosorbent assay in three groups of infertile women: women with TFI (n= 70), controls with normal fallopian tubes (control group 1, n= 92) and a subgroup of women with normal fallopian tubes and sero-positive for either chlamydial MOMP or chlamydial HSP60 (control group 2, n= 28). Serum levels of immunoglobulin (Ig)G1 and IgG3 antibodies against MOMP and HSP60 from C. trachomatis were elevated in patients with TFI compared with non-TFI individuals (group 1; P <0.001), while levels of IgG3 against MOMP and IgG1 against HSP60 were higher in the TFI group compared with control group 2 (P= 0.04 and P= 0.03, respectively). Levels of antibodies against human HSP60 did not differ between groups. Our findings confirm an association between TFI and antibodies to MOMP and HSP60 from C. trachomatis, suggesting antibody testing as a supplement in TFI diagnosis. No connection was observed between TFI and antibodies to human HSP60, pointing to an infectious rather than an autoimmune inflammation as the cause of TFI.

Context: Exogenous ketone body administration lowers circulating glucose levels but the underlying mechanisms are uncertain.Objective: We tested the hypothesis that administration of the ketone body β-hydroxybutyrate (βOHB) acutely increases insulin sensitivity via feedback suppression of circulating free fatty acid (FFA) levels.Methods: In a randomized, single-blinded crossover design, 8 healthy men were studied twice with a growth hormone (GH) infusion to induce lipolysis in combination with infusion of either βOHB or saline. Each study day comprised a basal period and a hyperinsulinemic-euglycemic clamp combined with a glucose tracer and adipose tissue and skeletal muscle biopsies.Results: βOHB administration profoundly suppressed FFA levels concomitantly with a significant increase in glucose disposal and energy expenditure. This was accompanied by a many-fold increase in skeletal muscle content of both βOHB and its derivative acetoacetate.Conclusion: Our data unravel an insulin-sensitizing effect of βOHB, which we suggest is mediated by concomitant suppression of lipolysis.

Abdominal obesity is associated with elevated postprandial triglycerides (TG), an independent risk factor for cardiovascular diseases. Previous studies show that whey protein (WP) and dietary fiber may separately reduce postprandial TG. However, few studies have investigated the long-term effects of WP and dietary fiber on postprandial TG. We aimed to investigate the separate and combined long-term effects of WP and dietary fiber from wheat bran on postprandial TG and markers of lipid metabolism in subjects with abdominal obesity. We conducted a 12-week, double-blind, randomized, controlled, parallel intervention study. In a 2 × 2 factorial design, 73 adults were randomized to receive 60 g/day of either WP hydrolysate or maltodextrin (MD) combined with high-fiber wheat bran products (HiFi; 30 g dietary fiber/day) or low-fiber refined wheat products (LoFi; 10 g dietary fiber/day). A high-fat meal test was conducted before and after the intervention. Sixty-five subjects were included in the final analyses. There were no differences between intervention groups in postprandial TG assessed as incremental area under the curve (iAUC). WP-LoFi had reduced postprandial TG assessed as total area under the curve (tAUC) and reduced fasting TG compared with all other groups, and reduced fasting apolipoprotein B-48 compared with MD-LoFi. There were no changes in lipoprotein lipase activity. Total cholesterol and apolipoprotein B-100 were reduced after WP intake compared with MD. Total cholesterol was increased after HiFi intake compared with LoFi. In conclusion, intake of WP in combination with low-fiber cereal products for 12 weeks had beneficial effects on postprandial TG tAUC and fasting TG, but not on postprandial TG iAUC in subjects with abdominal obesity. Combining WP with high-fiber wheat bran products did not improve lipid profile.

Growth hormone (GH) stimulates lipolysis, but the underlying mechanisms remain incompletely understood. We examined the effect of GH on the expression of lipolytic regulators in adipose tissue (AT). In a randomized, placebo-controlled, cross-over study, nine men were examined after injection of 1) a GH bolus and 2) a GH-receptor antagonist (pegvisomant) followed by four AT biopsies. In a second study, eight men were examined in a 2 × 2 factorial design including GH infusion and 36-h fasting with AT biopsies obtained during a basal period and a hyperinsulinemic-euglycemic clamp. Expression of GH-signaling intermediates and lipolytic regulators were studied by PCR and western blotting. In addition, mechanistic experiments in mouse models and 3T3-L1 adipocytes were performed. The GH bolus increased circulating free fatty acids (p < 0.0001) together with phosphorylation of signal transducer and activator of transcription 5 (STAT5) (p < 0.0001) and mRNA expression of the STAT5-dependent genes cytokine-inducible SH2-containing protein (CISH) and IGF-1 in AT. This was accompanied by suppressed mRNA expression of G0/G1 switch gene 2 (G0S2) (p = 0.007) and fat specific protein 27 (FSP27) (p = 0.002) and upregulation of phosphatase and tensin homolog (PTEN) mRNA expression (p = 0.03). Suppression of G0S2 was also observed in humans after GH infusion and fasting, as well as in GH transgene mice, and in vitro studies suggested MEK-PPARγ signaling to be involved. GH-induced lipolysis in human subjects in vivo is linked to downregulation of G0S2 and FSP27 and upregulation of PTEN in AT. Mechanistically, in vitro data suggest that GH acts via MEK to suppress PPARγ-dependent transcription of G0S2. ClinicalTrials.govNCT02782221 and NCT01209429.