Tanja C. Adam

Subcutaneous Adipose Tissue Macrophage Infiltration Is Associated With Hepatic and Visceral Fat Deposition, Hyperinsulinemia, and Stimulation of NF-κB Stress Pathway

OBJECTIVE To examine in obese young adults the influence of ethnicity and subcutaneous adipose tissue (SAT) inflammation on hepatic fat fraction (HFF), visceral adipose tissue (VAT) deposition, insulin sensitivity (SI), β-cell function, and SAT gene expression. RESEARCH DESIGN AND METHODS SAT biopsies were obtained from 36 obese young adults (20 Hispanics, 16 African Americans) to measure crown-like structures (CLS), reflecting SAT inflammation. SAT, VAT, and HFF were measured by magnetic resonance imaging, and SI and β-cell function (disposition index [DI]) were measured by intravenous glucose tolerance test. SAT gene expression was assessed using Illumina microarrays. RESULTS Participants with CLS in SAT (n = 16) were similar to those without CLS in terms of ethnicity, sex, and total body fat. Individuals with CLS had greater VAT (3.7 ± 1.3 vs. 2.6 ± 1.6 L; P = 0.04), HFF (9.9 ± 7.3 vs. 5.8 ± 4.4%; P = 0.03), tumor necrosis factor-α (20.8 ± 4.8 vs. 16.2 ± 5.8 pg/mL; P = 0.01), fasting insulin (20.9 ± 10.6 vs. 9.7 ± 6.6 mU/mL; P < 0.001) and glucose (94.4 ± 9.3 vs. 86.8 ± 5.3 mg/dL; P = 0.005), and lower DI (1,559 ± 984 vs. 2,024 ± 829 ×10−4 min−1; P = 0.03). Individuals with CLS in SAT exhibited upregulation of matrix metalloproteinase-9 and monocyte antigen CD14 genes, as well as several other genes belonging to the nuclear factor-κB (NF-κB) stress pathway. CONCLUSIONS Adipose tissue inflammation was equally distributed between sexes and ethnicities. It was associated with partitioning of fat toward VAT and the liver and altered β-cell function, independent of total adiposity. Several genes belonging to the NF-κB stress pathway were upregulated, suggesting stimulation of proinflammatory mediators.

Glucagon-like peptide-1 release and satiety after a nutrient challenge in normal-weight and obese subjects

The present study was conducted to assess whether glucagon-like peptide-1 (GLP-1) release and appetite after a breakfast with or without an additional galactose/guar gum stimulation is different in normal-weight compared with overweight/obese subjects. Twenty-eight overweight/obese (BMI 30.3 (sd 2.7) kg/m2; age 44.3 (sd 9.7) years) and thirty normal-weight subjects (BMI 22.8 (sd 1.4), age 31.5 (sd12.8) years) participated in a crossover study. Fasting and postprandial plasma GLP-1, insulin, glucose and free fatty acid concentrations were measured in response to either a galactose (50 g)/guar gum (2.5 g) load (836 kJ) and a standard breakfast (1.9 MJ; GG), or water (250 ml) and the standard breakfast (W) every 30 min relative to the ingestion for 120 min. Appetite was assessed using 100 mm visual analogue scales. GLP-1 concentrations were significantly increased after GG at 30 and 60 min compared with W in both groups. Plasma GLP-1 concentrations in the W condition were higher in normal-weight than overweight/obese subjects (P=0.03). No difference was observed in the GG condition between groups. Satiety was increased in normal-weight compared with overweight/obese subjects in the GG condition at 30 (P=0.02) and 60 (P=0.04) min. We conclude that after a standard breakfast with water, GLP-1 release was lower in the overweight/obese than the normal-weight subjects. However, postprandial GLP-1 release in overweight/obese subjects was no different from that of normal-weight subjects when galactose/guar gum was added to the breakfast. The latter was not mirrored by subjective feelings of satiety. Disturbed perception of the physiological feedback of a satiety hormone rather than disturbed feedback itself might contribute to obesity.

Is social jetlag associated with an adverse endocrine, behavioral, and cardiovascular risk profile?

Social jetlag represents the discrepancy between circadian and social clocks, which is measured as the difference in hours in midpoint of sleep between work days and free days. Previous studies have shown social jetlag to be associated with body mass index (BMI), glycated hemoglobin levels, heart rate, depressive symptoms, smoking, mental distress and alcohol use. The objective of our current study was to investigate, in a group of 145 apparently healthy participants (67 men and 78 women, aged 18-55 years, BMI 18-35 kg/m2), the prevalence of social jetlag and its association with adverse endocrine, behavioral and cardiovascular risk profiles as measured in vivo. participants with ≥2 h social jetlag had higher 5-h cortisol levels, slept less during the week, were more often physically inactive and had an increased resting heart rate, compared with participants who had ≤1 h social jetlag. We therefore concluded that social jetlag is associated with an adverse endocrine, behavioral and cardiovascular risk profile in apparently healthy participants. These adverse profiles put healthy participants at risk for development of metabolic diseases and mental disorders, including diabetes and depression, in the near future.

Randomized Controlled Trial to Improve Adiposity, Inflammation, and Insulin Resistance in Obese African-American and Latino Youth

The purpose of this study was to examine ethnic differences in the metabolic responses to a 16‐week intervention designed to improve insulin sensitivity (SI), adiposity, and inflammation in obese African‐American and Latino adolescents. A total of 100 participants (African Americans: n = 48, Latino: n = 52; age: 15.4 ± 1.1 years, BMI percentile: 97.3 ± 3.3) were randomly assigned to interventions: control (C; n = 30), nutrition (N; n = 39, 1×/week focused on decreasing sugar and increasing fiber intake), or nutrition + strength training (N+ST; n = 31, 2×/week). The following were measured at pre‐ and postintervention: strength, dietary intake, body composition (dual‐energy X‐ray absorptiometry/magnetic resonance imaging) and glucose/insulin indexes (oral glucose tolerance test (OGTT)/intravenous glucose tolerance test (IVGTT)) and inflammatory markers. Overall, N compared to C and N+ST reported significant improvements in SI (+16.5% vs. −32.3% vs. −6.9% respectively, P < 0.01) and disposition index (DI: +15.5% vs. −14.2% vs. −13.7% respectively, P < 0.01). N+ST compared to C and N reported significant reductions in hepatic fat fraction (HFF: −27.3% vs. −4.3% vs. 0% respectively, P < 0.01). Compared to N, N+ST reported reductions in plasminogen activator inhibitor‐1 (PAI‐1) (−38.3% vs. +1.0%, P < 0.01) and resistin (−18.7% vs. +11.3%, P = 0.02). There were no intervention effects for all other measures of adiposity or inflammation. Significant intervention by ethnicity interactions were found for African Americans in the N group who reported increases in total fat mass, 2‐h glucose and glucose incremental areas under the curve (IAUC) compared to Latinos (Ps < 0.05). These interventions yielded differential effects with N reporting favorable improvements in SI and DI and N+ST reporting marked reductions in HFF and inflammation. Both ethnic groups had significant improvements in metabolic health; however some improvements were not seen in African Americans.

Nutrient-stimulated glucagon-like peptide 1 release after body-weight loss and weight maintenance in human subjects

Glucagon-like peptide 1 (GLP-1) is a peptide hormone that is released in response to nutrient ingestion. Postprandial GLP-1 release has been reported to be attenuated in obese subjects, but reports on the effect of weight loss on GLP-1 are conflicting. The aim of the present study was to clarify the effect of a weight-loss period and a consecutive weight-maintenance period on nutrient-stimulated GLP-1 release in obese subjects. Nutrient-stimulated (standard breakfast; 1.9 MJ) GLP-1 release was investigated in thirty-two obese subjects on three occasions: before weight loss (T1) (BMI 30.0 (sd 2.5) kg/m(2)); after a 6-week very-low-energy diet (VLED) (T2) (BMI 27.6 (sd 2.3) kg/m(2)); after a 3-month weight-maintenance period (T3) (BMI 27.9 (sd 2.3) kg/m(2)). At each occasion, following a fasting blood sample the test meal was fed and blood was drawn every 30 min for 2 h relative to ingestion in order to determine plasma GLP-1, insulin, glucose and NEFA concentrations. Subjects lost 7 (sd 3.4) kg during the VLED (P<0.0001) and regained 1 (sd 3.2) kg during the weight-maintenance period (NS). The area under the curve for nutrient-stimulated plasma GLP-1 (pmol/l x h) was significantly decreased (P=0.01) at T2 (6.8 (sd 1)) compared with T1 (12.8 (sd 2.9)) and T3 (11.1 (sd 1.5)). Since we found a rebound of concentrations after a weight-maintenance period, decrease after weight loss seems to be transient and possibly due to a negative energy balance.

Increased sensitivity to food cues in the fasted state and decreased inhibitory control in the satiated state in the overweight

BACKGROUND Flexibility of food reward-related brain signaling (FRS) between food and nonfood stimuli may differ between overweight and normal-weight subjects and depend on a fasted or satiated state. OBJECTIVE The objective was to assess this flexibility in response to visual food and nonfood cues. DESIGN Twenty normal-weight [mean ± SEM BMI (in kg/m(2)) = 22.7 ± 0.2; mean ± SEM age = 22.4 ± 0.4 y] and 20 overweight (BMI = 28.1 ± 0.3; age = 24.0 ± 0.7 y) participants completed 2 fMRI scans. Subjects arrived in a fasted state and consumed a breakfast consisting of 20% of subject-specific energy requirements between 2 successive scans. A block paradigm and a food > nonfood contrast was used to determine FRS. RESULTS An overall stimulus × condition × subject group effect was observed in the anterior cingulate cortex (ACC) (P < 0.006, F((1,38)) = 9.12) and right putamen (P < 0.006, F((1,38)) = 9.27). In all participants, FRS decreased from the fasted to the satiated state in the cingulate (P < 0.005, t((39)) = 3.15) and right prefrontal cortex (PFC) (P < 0.006, t((39)) = 3.00). In the fasted state, they showed FRS in the PFC (P < 0.004, t((39)) = 3.17), left insula (P < 0.009, t((39)) = 2.95), right insula (P < 0.005, t((39)) = 3.12), cingulate cortex (P < 0.004, t((39)) = 3.21), and thalamus (P < 0.006, t((39)) = 2.96). In the satiated state, FRS was limited to the left insula (P < 0.005, t((39)) = 3.21), right insula (P < 0.006, t((39)) = 3.04), and cingulate cortex (P < 0.005, t((39)) = 3.15). Regarding subject group, in the fasted state, FRS in the ACC was more pronounced in overweight than in normal-weight subjects (P < 0.005, F((1,38)) = 9.71), whereas in the satiated state, FRS was less pronounced in overweight than in normal-weight subjects in the ACC (P < 0.006, F((1,38)) = 9.18) and PFC (P < 0.006, F((1,38)) = 8.86), which suggests lower inhibitory control in the overweight. CONCLUSION FRS was higher in the overweight in the satiated state; however, when sufficiently satiated, the overweight showed decreased inhibitory control signalling, which facilitates overeating. This trial was registered in the Dutch clinical trial register as NTR2174.

Cortisol Is Negatively Associated with Insulin Sensitivity in Overweight Latino Youth

CONTEXT AND OBJECTIVE The purpose of the present study was to investigate the cross-sectional and longitudinal associations of serum morning cortisol and aspects of insulin action in Latino children and adolescents (8-13 yr) at risk for type 2 diabetes. DESIGN AND PARTICIPANTS The present study includes a cross-sectional analysis in 211 participants and a longitudinal analysis in a subset of 143 participants. RESULTS At baseline, cortisol was negatively associated with fasting glucose (r = 0.23; P < 0.01), β-cell function (disposition index, r = -0.24; P < 0.05), and acute insulin response to glucose (r = -0.27; P < 0.05). Baseline cortisol was also significantly related to the change in insulin sensitivity over 1 yr (r = -0.23; P < 0.05). These results did not differ by Tanner stage or sex. CONCLUSIONS Cortisol contributes to the reduction in insulin sensitivity at an early age in Latino children and adolescents. Specifically, cortisol is negatively associated with potential compensatory mechanisms for insulin resistance, such as increased β-cell function and increased insulin release to a glucose challenge, by exacerbating the progression toward insulin resistance in this population. The results underline the relevance of glucocorticoid reduction for the prevention of metabolic disease in Latino children and adolescents.

Ethnic Differences in Insulin Action in Obese African-American and Latino Adolescents

INTRODUCTION African-American children have a greater acute insulin response to iv glucose (AIR) compared with Latino children despite a similar degree of insulin resistance and body composition. It is unclear whether African-Americans demonstrate an exaggerated insulin response to an oral glucose challenge and whether any differences are seen in more obese children in advanced pubertal development. PURPOSE Our objective was to compare glucose and insulin indices derived from an oral glucose tolerance test (OGTT) and iv glucose tolerance test (IVGTT) in sedentary, obese African-American (n=59) and Latino (n=83) adolescents. METHODS Glucose and insulin incremental area under the curve was measured during an OGTT, and AIR, insulin sensitivity, disposition index, and glucose effectiveness were assessed during an IVGTT. Body composition was assessed via dual-energy x-ray absorptiometry and magnetic resonance imaging. RESULTS From the OGTT, glucose and insulin IAUC were 29.1 and 22.5% lower (P=0.01) in African-Americans compared with Latino adolescents. From the IVGTT, insulin sensitivity and glucose effectiveness were 41.7% (P<0.01) and 50.0% (P=0.02) lower in African-Americans compared to Latinos. AIR (P=0.001) and disposition index (P=0.02) were 63.0 and 48.8% higher in African-Americans, respectively, compared with Latinos. These findings persisted after controlling for body composition and fat distribution. CONCLUSIONS There were marked differences in glucose and insulin indices derived from the OGTT and IVGTT. African-Americans were more insulin resistant as measured by the IVGTT compared with the Latino adolescents. However, the well-described hyperinsulinemia in response to iv glucose was not observed after oral glucose in African-American adolescents.

Sleep duration, sleep quality and body weight: parallel developments.

The increase in obesity, including childhood obesity, has developed over the same time period as the progressive decrease in self-reported sleep duration. Since epidemiological studies showed an inverse relationship between short or disturbed sleep and obesity, the question arose, how sleep duration and sleep quality are associated with the development of obesity. In this review, the current literature on these topics has been evaluated. During puberty, changes in body mass index (BMI) are inversely correlated to changes in sleep duration. During adulthood, this relationship remains and at the same time unfavorable metabolic and neuro-endocrinological changes develop, that promote a positive energy balance, coinciding with sleep disturbance. Furthermore, during excessive weight loss BMI and fat mass decrease, in parallel, and related with an increase in sleep duration. In order to shed light on the association between sleep duration, sleep quality and obesity, until now it only has been shown that diet-induced body-weight loss and successive body-weight maintenance contribute to sleep improvement. It remains to be demonstrated whether body-weight management and body composition improve during an intervention concomitantly with spontaneous sleep improvement compared with the same intervention without spontaneous sleep improvement.

Activity-induced GLP-1 release in lean and obese subjects

The aim of the study was to determine whether physical activity stimulates GLP-1 release on the short-term in normal weight and in obese subjects compared to rest and, furthermore, whether modest weight loss affects GLP-1 release or sensitivity in the obese. Normal weight (n=28; 12 males, 16 females; BMI 22.9+/-1.4; age 35+/-12.7), as well as obese subjects (n=27; 21 males, 6 females; BMI 30.9+/-2.7; age 47.1+/-11.86) were tested in a resting and a physical activity condition. Obese subjects were matched over two groups for a weight loss period of 3 months. After weight loss, the tests were repeated. The area under the curve (AUC pmol/lxmin) for GLP-1 concentrations was significantly increased in the physical activity condition compared to rest in lean subjects (P=0.05) as well as in the obese subjects after weight loss (P<0.05), but not in the obese subjects before weight loss. Physical activity-stimulated GLP-1 release in lean and obese subjects after a weight loss period supports the idea of a neuroendocrine loop in addition to distal-intestinal stimulation of GLP-1 release. Modest weight loss might be effective for increasing GLP-1 sensitivity to acute stimulation.