Impact of fibroblast growth factor 21 on the secretome of human perivascular preadipocytes and adipocytes: a targeted proteomics approach.

Context: Perivascular adipose tissue (PVAT) is suggested to impact on vascular cells via humoral factors, possibly contributing to endothelial dysfunction and atherosclerosis.

Objective: To address whether the hepatokine fibroblast growth factor (FGF) 21 affects the PVAT secretome.

Methods: Human perivascular (pre)adipocytes were subjected to targeted proteomics and whole-genome gene expression analysis.

Tbc1d1 deletion suppresses obesity in leptin-deficient mice.

Background: Variants in the gene TBC1D1 have been previously associated with obesity-related traits in several species, including humans, mice, rabbits and chicken. While in humans variants in TBC1D1 were linked to obesity, disruption of the Tbc1d1 gene reduced body weight in mice. TBC1D1 has been identified as a regulator of insulin-dependent glucose transport in skeletal muscle, however, its role in energy homeostasis in the obese state remains unclear.

Whole-exome sequencing identifies mutations of TBC1D1 encoding a Rab-GTPase-activating protein in patients with congenital anomalies of the kidneys and urinary tract (CAKUT).

Congenital anomalies of the kidneys and urinary tract (CAKUT) are genetically highly heterogeneous leaving most cases unclear after mutational analysis of the around 30 causative genes known so far. Assuming that phenotypes frequently showing dominant inheritance, such as CAKUT, can be caused by de novo mutations, de novo analysis of whole-exome sequencing data was done on two patient-parent-trios to identify novel CAKUT genes. In one case, we detected a heterozygous de novo frameshift variant in TBC1D1 encoding a Rab-GTPase-activating protein regulating glucose transporter GLUT4 translocation.

Mental health problems among adolescents with early-onset and long-duration type 1 diabetes and their association with quality of life: a population-based survey.

Objective: To evaluate mental health problems and associations between mental health problems and health-related quality of life in adolescents with type 1 diabetes in comparison with the general population.

Method: A total of 629 11- to 17-year-olds with early-onset and long-lasting type 1 diabetes and their parents completed comprehensive questionnaires. Mental health was assessed using the parent- and self-report versions of the Strengths and Difficulties Questionnaire (SDQ).

Conventional knockout of Tbc1d1 in mice impairs insulin- and AICAR-stimulated glucose uptake in skeletal muscle.

In the obesity-resistant SJL mouse strain, we previously identified a naturally occurring loss-of-function mutation in the gene for Tbc1d1. Characterization of recombinant inbred mice that carried the Tbc1d1(SJL) allele on a C57BL/6J background indicated that loss of TBC1D1 protects from obesity, presumably by increasing the use of fat as energy source. To provide direct functional evidence for an involvement of TBC1D1 in energy substrate metabolism, we generated and characterized conventional Tbc1d1 knockout mice.

Fatty acids modulate cytokine and chemokine secretion of stimulated human whole blood cultures in diabetes.

Fatty acids, uric acid and glucose are thought to contribute to subclinical inflammation associated with diabetes mellitus. We tested whether co-incubation of free fatty acids and uric acid or glucose influences the secretion of immune mediators from stimulated human whole blood in vitro. Fresh whole blood samples from 20 healthy subjects, 20 patients with type 1 diabetes and 23 patients with type 2 diabetes were incubated for 24 h with palmitic acid (PAL), linolenic acid (LIN) or eicosapentaenoic acid (EPA) alone or together with elevated concentrations of uric acid or glucose.

Risk for high depressive symptoms in diagnosed and previously undetected diabetes: 5-year follow-up results of the Heinz Nixdorf Recall study.

Objective: The objective of this study was to determine the risk for the development of high depressive symptoms in study participants with diagnosed and previously undetected diabetes mellitus compared to those without diabetes in a prospective population-based cohort study in Germany.

Methods: We estimated the 5-year cumulative incidence of high depressive symptoms in participants without high depressive symptoms at baseline (n = 3,633, 51.4% men, mean age (SD) 59.

Adaptive immunity in obesity and insulin resistance.

Obesity is the hallmark of the metabolic syndrome and predisposes patients to the development of major chronic metabolic diseases including type 2 diabetes mellitus. Adipose tissue expansion in obesity is characterized by increasing infiltration of proinflammatory immune cells into adipose tissue causing chronic, low-grade inflammation. Phenotypic switching of macrophages is an important mechanism of adipose tissue inflammation, and there is involvement of cells from the adaptive immune system in this process.

Diabetes incidence does not differ between subjects with and without high depressive symptoms--5-year follow-up results of the Heinz Nixdorf Recall Study.

Aims: Cross-sectional studies have consistently reported evidence for an association between diabetes and depressive disorders. However, only limited prospective studies have examined this association, reporting conflicting results. In a population-based cohort study, we compared cumulative incidences of diabetes between participants with and without high depressive symptoms.

Heat shock protein 60 as a mediator of adipose tissue inflammation and insulin resistance.

The stress protein heat shock protein 60 (Hsp60) induces secretion of proinflammatory mediators from murine adipocytes. This study aimed to study Hsp60 as a mediator of adipose tissue inflammation and skeletal muscle cell (SkMC) insulin sensitivity and to quantify plasma Hsp60 concentrations in lean and obese individuals. Regulation of Hsp60 release and Hsp60-induced cytokine secretion and signaling was measured in human adipocytes and SkMCs.

Prevalence and risk factors of neuropathic pain in survivors of myocardial infarction with pre-diabetes and diabetes. The KORA Myocardial Infarction Registry.

The lowest glycemic threshold for and the risk factors associated with neuropathic pain have not been established. The aim of this study was to determine the prevalence and risk factors of neuropathic pain in survivors of myocardial infarction with diabetes, impaired glucose tolerance (IGT), impaired fasting glucose (IFG), normal glucose tolerance (NGT). Subjects aged 25-74 years with diabetes (n=214) and controls matched for age and sex (n=212) from the population-based KORA (Cooperative Health Research in the Region of Augsburg) Myocardial Infarction Registry were assessed for neuropathic pain by the Michigan Neuropathy Screening Instrument using its pain-relevant questions and an examination score cutpoint >2.