Lower circulating omentin-1 is independently linked to subclinical hypothyroidism reflecting cardiometabolic risk: an observational case-control and interventional, longitudinal study.

BACKGROUND: Omentin-1, a newly discovered adipokine, is implicated in the modulation of the adipose phenotype, ameliorating systemic metabolism and exhibiting anti-atherogenic, anti-oxidative, cardioprotective, anti-inflammatory and insulin-sensitizing properties. Our goal was to explore circulating omentin-1 in subclinical hypothyroidism (SH) and determine its correlations with cardiometabolic risk factors. METHODS: In a large case-control and interventional longitudinal study, serum omentin-1, metabolic and lipid parameters, inflammatory biomarkers, classic adipocytokines and cardiovascular risk factors were assessed in 120 consecutive patients with SH and 120 healthy controls matched on age, gender and date of blood draw. Sixteen patients with SH were administered L-T4 and, after six months, circulating omentin-1 and other biomarkers were determined. RESULTS: SH subjects presented significantly decreased circulating omentin-1 than control individuals (P<0.001). In all study participants, omentin-1 was negatively correlated with TSH, anti-thyroid antibodies, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, adipokines and cardiovascular risk factors, including Framingham score and apolipoprotein B. Omentin-1 was positively associated with adiponectin and HDL-C. Circulating omentin-1 was independently associated with SH occurrence, above and beyond clinical and cardiometabolic factors (P=0.04). TSH was a negative independent predictor of serum omentin-1 levels (P<0.001). L-T4 treatment did not alter considerably the lower omentin-1 levels in treated SH patients (P=0.07). CONCLUSIONS: Omentin-1 may be a useful non-invasive biomarker reflecting cardiometabolic risk as well as a promising therapeutic target. More mechanistic and larger prospective studies shedding light on the pathogenetic role of omentin-1 in SH are required to confirm these findings.

Circulating leptin, soluble leptin receptor and free leptin index in critically ill patients with sepsis: a prospective observational study.

BACKGROUND: Leptin, the prototype adipokine, exerts immunomodulatory actions being implicated in inflammatory responses during sepsis. Clinical evidence regarding its role in sepsis has been contradictory, while free leptin has not been studied. The aim of this study was to jointly investigate circulating total leptin, its soluble receptor (sOB-R), and free leptin, as well as their kinetics in critically ill patients with sepsis regarding their diagnostic and prognostic value. METHODS: In a prospective study, serum total leptin, sOB-R and free leptin index (FLI) were determined in 102 critically ill patients with sepsis within 48 hours from sepsis onset and one week after enrollment, and in 102 age and gender-matched healthy controls. RESULTS: Upon enrolment, total leptin, sOB-R and FLI were significantly higher in septic patients compared to controls and they were positively correlated with sepsis severity scores, while they presented a significant decrease during the first week (P<0.001). The decrease in total leptin and sOB-R was significantly higher in patients with sepsis compared to septic shock and in survivors compared to non-survivors at 28 days (P<0.001). Higher serum total leptin was independently associated with survival at 28 days (enrollment: HR 0.86, P=0.03; one week after: HR 0.77, P<0.001). Higher kinetics of total leptin (but not FLI) was independently associated with survival after adjustment (HR: 0.48, P=0.001). CONCLUSIONS: Higher circulating total leptin and its higher kinetics during the first week from sepsis onset independently predict 28-day survival in critically ill patients. Free leptin did not present any additional diagnostic and prognostic value in sepsis.

Adiponectin as a biomarker linking obesity and adiposopathy to hematologic malignancies.

Higher body mass index and adiposopathy have been associated with increased risk of hematologic malignancies such as leukemia, multiple myeloma, myeloproliferative disorders, Hodgkin's and non-Hodgkin's lymphoma, and myelodysplastic syndromes. Adiponectin is a multimeric protein of the white adipose tissue presenting anti-inflammatory, insulin-sensitizing, anti-atherogenic, cardioprotective, and anti-neoplastic properties. Its anti-neoplastic actions are manifested via two mechanisms: (i) direct action on tumor cells by enhancing receptor-mediated signaling pathways and (ii) indirect action by regulating inflammatory responses, influencing cancer angiogenesis, and modulating insulin sensitivity at the target tissue site. In the bone marrow milieu, adiponectin and its main receptors are expressed by the majority of bone marrow stromal cell populations influencing hematopoietic stem cells function. Adiponectin may represent a molecular mediator relating adiposopathy with leukemogenesis and myelomagenesis. Several epidemiological studies conducted to date relate hypoadiponectinemia to the risk of myeloid-derived hematopoietic cancer and multiple myeloma. Adiponectin may be a promising biomarker with potential diagnostic and prognostic utility in determining the likelihood of myeloma and leukemia progression in certain cohorts of monoclonal gammopathy of undetermined significance patients and in myeloid hematologic malignancies, respectively. This review summarizes experimental and epidemiologic data regarding the role of adiponectin in hematologic malignancies in the context of adiposopathy. Enhancement of endogenous adiponectin, adiponectin replacement, or manipulation of adiponectin receptor sensitivity may be an attractive goal for prevention and an effective therapeutic strategy against hematopoietic cancer, specifically in overweight/obese individuals. Further studies are required to elucidate the role of the bone marrow microenvironment adiponectin in complex interactions involved in preleukemic and leukemic states.