Childhood social preference and adolescent insulin resistance: Accounting for the indirect effects of obesity

Adipose tissue (AT) inflammation is an emerging factor contributing to cardiovascular disease. STAT4 is a transcription factor expressed in adipocytes and in immune cells and contributes to AT inflammation and insulin resistance in obesity. The objective of this study was to determine the effect of STAT4 deficiency on visceral and peri-aortic AT inflammation in a model of atherosclerosis without obesity. Stat4−/−Apoe−/− mice and Apoe−/− controls were kept either on chow or Western diet for 12 weeks. Visceral and peri-aortic AT were collected and analyzed for immune composition by flow cytometry and for cytokine/chemokine expression by real-time PCR. Stat4−/−Apoe−/− and Apoe−/− mice had similar body weight, plasma glucose, and lipids. Western diet significantly increased macrophage, CD4+, CD8+, and NK cells in peri-aortic and visceral fat in Apoe−/− mice. In contrast, in Stat4−/−Apoe−/− mice, a Western diet failed to increase the percentage of immune cells infiltrating the AT. Also, IL12p40, TNFa, CCL5, CXCL10, and CX3CL1 were significantly reduced in the peri-aortic fat in Stat4−/−Apoe−/− mice. Importantly, Stat4−/−Apoe−/− mice on a Western diet had significantly reduced plaque burden vs Apoe−/− controls. In conclusion, STAT4 deletion reduces inflammation in peri-vascular and visceral AT and this may contribute via direct or indirect effects to reduced atheroma formation.

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Indirect Effects of a Cognitive-Behavioral Intervention on Adolescent Weight and Insulin Resistance Through Decreasing Depression in a Randomized Controlled Trial

Journal of Pediatric Psychology ◽

10.1093/jpepsy/jsz064 ◽

2019 ◽

Vol 44 (10) ◽

pp. 1163-1173 ◽

Cited By ~ 4

Author(s):

Lauren D Gulley ◽

Lauren B Shomaker ◽

Nichole R Kelly ◽

Kong Y Chen ◽

Eric Stice ◽

...

Keyword(s):

Insulin Resistance ◽

At Risk ◽

Randomized Controlled Trial ◽

Indirect Effects ◽

Controlled Trial ◽

Cognitive Behavioral ◽

Depression Symptoms ◽

Targeted Prevention ◽

Glucose Testing ◽

Randomized Controlled

Abstract Objective Depression is linked to excess weight, insulin resistance, and type 2 diabetes (T2D). We previously reported that in adolescent girls at-risk for T2D with moderately elevated depression, randomization to cognitive-behavioral therapy (CBT) produced greater decreases in depression at post-treament and greater decreases in fasting/2-h insulin at 1 year, compared to health education (HE). The current study is a secondary analysis of this parallel-group randomized controlled trial. We examined whether decreasing depression explained intervention effects on body composition and insulin outcomes. We hypothesized that decreases in depression would be an explanatory mediator and that indirect effects would be strongest at higher levels of baseline depression. Methods Participants were 12–17 years girls with overweight/obesity and family history of T2D randomized to 6-week group CBT (n = 58) or HE (n = 61). Procedures took place at an outpatient pediatric clinic. At baseline, post-treatment, and 1 year, adolescents completed the Center for Epidemiologic Studies-Depression Scale to assess depression symptoms; body mass index (BMI [kg/m2]) was measured from height/fasting weight; insulin resistance was derived from 2-h oral glucose testing. Adiposity was assessed with dual-energy X-ray absorptiometry at baseline and 1 year. Indirect effects of intervention were tested on 1-year changes in BMI, adiposity, and insulin through decreases in depression. Baseline depression was tested as a moderator of mediation. Results There was an indirect effect of CBT on decreased 1-year fasting insulin via decreases in depression during treatment, among adolescents with more elevated baseline depression. Conclusions Decreasing elevated depression may be one mechanism in the targeted prevention of T2D in at-risk adolescents.

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