Salsalate treatment improves glycemia without altering adipose tissue in nondiabetic obese hispanics.

ObjectiveSalsalate treatment has well-known effects on improving glycemia, and the objective of this study was to examine whether the mechanism of this effect was related to changes in adipose tissue.MethodsA randomized double-blind and placebo-controlled trial in obese Hispanics (18-35 years) was conducted. The intervention consisted of 4 g day(-1) of salsalate (n = 11) versus placebo (n = 13) for 4 weeks. Outcome measures included glycemia, adiposity, ectopic fat, and adipose tissue gene expression and inflammation.ResultsIn those receiving salsalate, plasma fasting glucose decreased by 3.4% (P < 0.01), free fatty acids decreased by 42.5% (P = 0.06), and adiponectin increased by 27.7% (P < 0.01). Salsalate increased insulin AUC by 38% (P = 0.01) and HOMA-B by 47.2% (P < 0.01) while estimates of insulin sensitivity/resistance were unaffected. These metabolic improvements occurred without changes in total, abdominal, visceral, or liver fat. Plasma markers of inflammation/immune activation were unchanged following salsalate. Salsalate had no effects on adipose tissue including adipocyte size, presence of crown-like structures, or gene expression of adipokines, immune cell markers, or cytokines downstream of NF-κB with the exception of downregulation of IL-1β (P < 0.01).ConclusionsFindings suggest that metabolic improvements in response to salsalate occurred without alterations in adiposity, ectopic fat, or adipose tissue gene expression and inflammation

Early development of negative and positive affect: Implications for ADHD symptomatology across three birth cohorts

High levels of early emotionality (of either negative or positive valence) are hypothesized to be important precursors to early psychopathology, with attention-deficit/hyperactivity disorder (ADHD) a prime early target. The positive and negative affect domains are prime examples of Research Domain Criteria (RDoC) concepts that may enrich a multilevel mechanistic map of psychopathology risk. Utilizing both variable-centered and person-centered approaches, the current study examined whether levels and trajectories of infant negative and positive emotionality, considered either in isolation or together, predicted children's ADHD symptoms at 4 to 8 years of age. In variable-centered analyses, higher levels of infant negative affect (at as early as 3 months of age) were associated with childhood ADHD symptoms. Findings for positive affect failed to reach statistical threshold. Results from person-centered trajectory analyses suggest that additional information is gained by simultaneously considering the trajectories of positive and negative emotionality. Specifically, only when exhibiting moderate, stable or low levels of positive affect did negative affect and its trajectory relate to child ADHD symptoms. These findings add to a growing literature that suggests that infant negative emotionality is a promising early life marker of future ADHD risk and suggest secondarily that moderation by positive affectivity warrants more consideration.</p

Relationship between psychological stress and ghrelin concentrations in pregnant women with overweight or obesity.

Exposure to, perception of, and response to stress have all been shown to influence appetite and dietary behaviors in non-pregnancy human and animal studies, mediated in part by the appetite stimulating hormone ghrelin. Yet, the impact of prenatal stress on biological pathways associated with appetite in the context of pregnancy is not well understood. The objective of this study was to assess the relationship between these layered dimensions of stress with fasting and postprandial plasma ghrelin concentrations among Hispanic pregnant women with overweight or obesity, a population known to experience heightened levels of stress. Thirty-three non-diabetic Hispanic women with pre-pregnancy body mass index of 25.0-34.9&nbsp;kg/m2 participated in a crossover study at 28-32 weeks' gestation. At each visit, participants provided fasting blood and saliva samples, consumed a standardized mixed-meal, and completed a 15-minute task: friendly conversation (control) or the Trier Social Stress Test (experimental stress exposure). Six timed blood and saliva samples were collected up to 2&nbsp;h from baseline and assayed for ghrelin and cortisol, respectively, and area-under-the-curve (AUC) values were computed. Day-to-day stress levels were assessed by the Perceived Stress Scale. Physiological and psychological stress reactivity was determined by cortisol AUC and change in self-reported affect state, respectively, during the experimental stress visit. Maternal perceived stress was positively associated with ghrelin concentrations in the fasted (β&nbsp;=&nbsp;0.06, p&nbsp;=&nbsp;0.02) and postprandial state (β&nbsp;=&nbsp;0.05, p&nbsp;=&nbsp;0.02). Mean ghrelin AUC was not significantly different following acute stress versus control. Measures of acute stress reactivity were not associated with ghrelin AUC. Contrary to our hypothesis, among Hispanic pregnant women with overweight and obesity, exposure to an acute stress induction task did not alter postprandial ghrelin concentrations, and changes in individual psychological and physiological stress reactivity did not associate with postprandial ghrelin. However, our findings suggest that maternal report of general perceived stress over the last month is associated with higher fasting and postprandial ghrelin concentrations. Differences in the effects of short-term stress exposure versus day-to-day perception of stress on appetite and food intake in pregnancy deserves further investigation

Developmental programming of mitochondrial biology: a conceptual framework and review

Research on mechanisms underlying the phenomenon of developmental programming of health and disease has focused primarily on processes that are specific to cell types, organs and phenotypes of interest. However, the observation that exposure to suboptimal or adverse developmental conditions concomitantly influences a broad range of phenotypes suggests that these exposures may additionally exert effects through cellular mechanisms that are common, or shared, across these different cell and tissue types. It is in this context that we focus on cellular bioenergetics and propose that mitochondria, bioenergetic and signalling organelles, may represent a key cellular target underlying developmental programming. In this review, we discuss empirical findings in animals and humans that suggest that key structural and functional features of mitochondrial biology exhibit developmental plasticity, and are influenced by the same physiological pathways that are implicated in susceptibility for complex, common age-related disorders, and that these targets of mitochondrial developmental programming exhibit long-term temporal stability. We conclude by articulating current knowledge gaps and propose future research directions to bridge these gaps

Rate of Gestational Weight Gain and Glucose-Insulin Metabolism Among Hispanic Pregnant Women With Overweight and Obesity.

ContextHispanic women are at elevated risk of gestational glucose intolerance and postpartum type 2 diabetes compared with non-Hispanic White women. Identification of potentially modifiable factors contributing to this trajectory of beta-cell dysfunction is warranted.ObjectiveWe aimed to determine the association between rate of gestational weight gain (rGWG) and glucose-insulin metabolism in Hispanic pregnant women with overweight and obesity.MethodsThis cross-sectional, observational study, conducted from 2018-2020 at the clinical research center at University of California, Irvine, included 33 nondiabetic Hispanic pregnant women at 28 to 30 weeks' gestation with pre-pregnancy body mass index (BMI) 25.0 to 34.9 kg/m2. Participants consumed a standardized liquid mixed meal after an overnight fast. Serial blood samples were collected at fasting and up to 2 hours postprandial. The glucose and insulin area under the curve (AUC), insulin sensitivity index (ISI) and insulin secretion sensitivity index (ISSI)-2 were computed.ResultsAverage rGWG (0.36 ± 0.22 kg/week) was classified as excessive in 60% of women. While rGWG was not associated with the glucose or insulin AUC or ISI, it accounted for 13.4% of the variance in ISSI-2 after controlling for covariates (maternal age, parity, and pre-pregnancy BMI); for each 1 unit increase in rGWG, ISSI-2 decreased 2.1 units (P = 0.015).ConclusionEven in the absence of gestational diabetes, rGWG was inversely associated with beta-cell function in a high-risk population of Hispanic pregnant women with overweight and obesity. Beta-cell decline is an established risk factor for transition to type 2 diabetes, and these cross-sectional findings highlight rGWG as a potentially modifiable contributor to this process

Modifying Influence of Dietary Sugar in the Relationship Between Cortisol and Visceral Adipose Tissue in Minority Youth

Objective—Cortisol has been associated with preferential visceral adipose tissue (VAT) deposition; however findings in humans are mixed, which may be clarified when diet is considered. Design and Methods—Participants included 165 African American and Latino, overweight adolescents (BMI % 97.2±3.2%, ages 13-18, 67 % Latino, 66 % female). Body composition was determined by DEXA, abdominal fat depots (VAT, subcutaneous (SAT)) by multiple-slice MRI, time-controlled serum sample to measure cortisol, and 2-day multi-pass 24-hour dietary recall. Linear regression analysis examined the cross-sectional relationship between cortisol, and the interaction of diet and cortisol on adiposity measures. Sex, race, age and total body fat were a priori covariates. Results—There was a significant interaction between cortisol and sugar (total and added) in the prediction of VAT (pinteraction&lt;=0.05). Amongst participants with high total or added-sugar intake, cortisol was significantly associated with VAT (β=0.031 p&lt;0.001; β=0.026 p&lt;0.001), with no relationship in low consumers of total or added-sugar. Conclusion—Dietary sugar may play an important role in modifying the relationship between cortisol and VAT, such that cortisol is significantly associated with elevated VAT under conditions of high sugar intake