Title: A Miniaturized MicroRNA Sensor Identifies Targets Associated with Weight Loss in a Diet and Exercise Intervention among Healthy Overweight Individuals
Weight loss through dietary and exercise intervention is commonly prescribed but is not effective for all individuals. Recent studies have demonstrated that circulating microRNA (miR) biomarkers could potentially be used to identify individuals who will likely lose weight through diet and exercise and attain a healthy body weight. However, accurate detection of miRs in clinical samples is difficult, error-prone, and expensive. To address this issue, we recently developed iLluminate—a low-cost and highly sensitive miR sensor suitable for point-of-care testing. To investigate if miR testing and iLluminate can be used in real-world obesity applications, we developed a pilot diet and exercise intervention and utilized iLluminate to evaluate miR biomarkers. We evaluated the expression of miRs-140, -935, -let-7b, and -99a, which are biomarkers for fat loss, energy metabolism, and adipogenic differentiation. Responders lost more total mass, tissue mass, and fat mass than non-responders. miRs-140, -935, -let-7b, and -99a, collectively accounted for 6.9% and 8.8% of the explained variability in fat and lean mass, respectively. At the level of the individual coefficients, miRs-140 and -935 were significantly associated with fat loss. Collectively, miRs-140 and -935 provide an additional degree of predictive capability in body mass and fat mass alternations. more »« less
Asare-Bediako, Bright; Noothi, Sunil; Li Calzi, Sergio; Athmanathan, Baskaran; Vieira, Cristiano; Adu-Agyeiwaah, Yvonne; Dupont, Mariana; Jones, Bryce; Wang, Xiaoxin; Chakraborty, Dibyendu; et al
(, Cells)
null
(Ed.)
We sought to delineate the retinal features associated with the high-fat diet (HFD) mouse, a widely used model of obesity. C57BL/6 mice were fed either a high-fat (60% fat; HFD) or low-fat (10% fat; LFD) diet for up to 12 months. The effect of HFD on body weight and insulin resistance were measured. The retina was assessed by electroretinogram (ERG), fundus photography, permeability studies, and trypsin digests for enumeration of acellular capillaries. The HFD cohort experienced hypercholesterolemia when compared to the LFD cohort, but not hyperglycemia. HFD mice developed a higher body weight (60.33 g vs. 30.17g, p < 0.0001) as well as a reduced insulin sensitivity index (9.418 vs. 62.01, p = 0.0002) compared to LFD controls. At 6 months, retinal functional testing demonstrated a reduction in a-wave and b-wave amplitudes. At 12 months, mice on HFD showed evidence of increased retinal nerve infarcts and vascular leakage, reduced vascular density, but no increase in number of acellular capillaries compared to LFD mice. In conclusion, the HFD mouse is a useful model for examining the effect of prediabetes and hypercholesterolemia on the retina. The HFD-induced changes appear to occur slower than those observed in type 2 diabetes (T2D) models but are consistent with other retinopathy models, showing neural damage prior to vascular changes.
Belliveau, Jessica; Thompson, Will; Papoutsakis, Eleftherios T
(, Biotechnology and Bioengineering)
Abstract Chinese hamster ovary (CHO) cells release and exchange large quantities of extracellular vesicles (EVs). EVs are highly enriched in microRNAs (miRs, or miRNAs), which are responsible for most of their biological effects. We have recently shown that the miR content of CHO EVs varies significantly under culture stress conditions. Here, we provide a novel stoichiometric (“per‐EV”) quantification of miR and protein levels in large CHO EVs produced under ammonia, lactate, osmotic, and age‐related stress. Each stress resulted in distinct EV miR levels, with selective miR loading by parent cells. Our data provide a proof of concept for the use of CHO EV cargo as a diagnostic tool for identifying culture stress. We also tested the impact of three select miRs (let‐7a, miR‐21, and miR‐92a) on CHO cell growth and viability. Let‐7a—abundant in CHO EVs from stressed cultures—reduced CHO cell viability, while miR‐92a—abundant in CHO EVs from unstressed cultures—promoted cell survival. Overexpression of miR‐21 had a slight detrimental impact on CHO cell growth and viability during late exponential‐phase culture, an unexpected result based on the reported antiapoptotic role of miR‐21 in other mammalian cell lines. These findings provide novel relationships between CHO EV cargo and cell phenotype, suggesting that CHO EVs may exert both pro‐ and antiapoptotic effects on target cells, depending on the conditions under which they were produced.
ABSTRACT The unfolded protein response (UPR) is involved in the pathogenesis of metabolic disorders, yet whether variations in the UPR among individuals influence the propensity for metabolic disease remains unexplored. Using outbred deer mice as a model, we show that the intensity of UPR in fibroblasts isolated early in life predicts the extent of body weight gain after high-fat diet (HFD) administration. Contrary to those with intense UPR, animals with moderate UPR in fibroblasts and therefore displaying compromised stress resolution did not gain body weight but developed inflammation, especially in the skin, after HFD administration. Fibroblasts emerged as potent modifiers of this differential responsiveness to HFD, as indicated by the comparison of the UPR profiles of fibroblasts responding to fatty acids in vitro, by correlation analyses between UPR and proinflammatory cytokine-associated transcriptomes, and by BiP (also known as HSPA5) immunolocalization in skin lesions from animals receiving HFD. These results suggest that the UPR operates as a modifier of an individual's propensity for body weight gain in a manner that, at least in part, involves the regulation of an inflammatory response by skin fibroblasts. This article has an associated First Person interview with the first author of the paper.
Swendeman, Dallas; Comulada, Warren Scott; Koussa, Maryann; Worthman, Carol M; Estrin, Deborah; Rotheram-Borus, Mary Jane; Ramanathan, Nithya
(, JMIR mHealth and uHealth)
Background Multiple strategies can be used when self-monitoring diet, physical activity, and perceived stress, but no gold standards are available. Although self-monitoring is a core element of self-management and behavior change, the success of mHealth behavioral tools depends on their validity and reliability, which lack evidence. African American and Latina mothers in the United States are high-priority populations for apps that can be used for self-monitoring of diet, physical activity, and stress because the body mass index (BMI) of mothers typically increases for several years after childbirth and the risks of obesity and its’ sequelae diseases are elevated among minority populations. Objective To examine the intermethod reliability and concurrent validity of smartphone-based self-monitoring via ecological momentary assessments (EMAs) and use of daily diaries for diet, stress, and physical activity compared with brief recall measures, anthropometric biomeasures, and bloodspot biomarkers. Methods A purposive sample (n=42) of primarily African American (16/42, 39%) and Latina (18/42, 44%) mothers was assigned Android smartphones for using Ohmage apps to self-monitor diet, perceived stress, and physical activity over 6 months. Participants were assessed at 3- and 6-month follow-ups. Recall measures included brief food frequency screeners, physical activity assessments adapted from the National Health and Nutrition Examination Survey, and the nine-item psychological stress measure. Anthropometric biomeasures included BMI, body fat, waist circumference, and blood pressure. Bloodspot assays for Epstein–Barr virus and C-reactive protein were used as systemic load and stress biomarkers. EMAs and daily diary questions assessed perceived quality and quantity of meals, perceived stress levels, and moderate, vigorous, and light physical activity. Units of analysis were follow-up assessments (n=29 to n=45 depending on the domain) of the participants (n=29 with sufficient data for analyses). Correlations, R2 statistics, and multivariate linear regressions were used to assess the strength of associations between variables. Results Almost all participants (39/42, 93%) completed the study. Intermethod reliability between smartphone-based EMAs and diary reports and their corresponding recall reports was highest for stress and diet; correlations ranged from .27 to .52 (P<.05). However, it was unexpectedly low for physical activity; no significant associations were observed. Concurrent validity was demonstrated for diet EMAs and diary reports on systolic blood pressure (r=−.32), C-reactive protein level (r=−.34), and moderate and vigorous physical activity recalls (r=.35 to.48), suggesting a covariation between healthy diet and physical activity behaviors. EMAs and diary reports on stress were not associated with Epstein–Barr virus and C-reactive protein level. Diary reports on moderate and vigorous physical activity were negatively associated with BMI and body fat (r=−.35 to −.44, P<.05). Conclusions Brief smartphone-based EMA use may be valid and reliable for long-term self-monitoring of diet, stress, and physical activity. Lack of intermethod reliability for physical activity measures is consistent with prior research, warranting more research on the efficacy of smartphone-based self-monitoring of self-management and behavior change support.
Dragan, Morgan; Chen, Zeyu; Li, Yumei; Le, Johnny; Sun, Peng; Haensel, Daniel; Sureshchandra, Suhas; Pham, Anh; Lu, Eddie; Pham, Katherine Thanh; et al
(, EMBO reports)
Abstract Skin epidermis constitutes the outer permeability barrier that protects the body from dehydration, heat loss, and myriad external assaults. Mechanisms that maintain barrier integrity in constantly challenged adult skin and how epidermal dysregulation shapes the local immune microenvironment and whole‐body metabolism remain poorly understood. Here, we demonstrate that inducible and simultaneous ablation of transcription factor‐encodingOvol1andOvol2in adult epidermis results in barrier dysregulation through impacting epithelial‐mesenchymal plasticity and inflammatory gene expression. We find that aberrant skin immune activation then ensues, featuring Langerhans cell mobilization and T cell responses, and leading to elevated levels of secreted inflammatory factors in circulation. Finally, we identify failure to gain body weight and accumulate body fat as long‐term consequences of epidermal‐specificOvol1/2loss and show that these global metabolic changes along with the skin barrier/immune defects are partially rescued by immunosuppressant dexamethasone. Collectively, our study reveals key regulators of adult barrier maintenance and suggests a causal connection between epidermal dysregulation and whole‐body metabolism that is in part mediated through aberrant immune activation.
Jayasooriya, Vidura, Johnson, Nathaniel, Bradley, Adam, Kotarsky, Christopher, Jepng’etich, Lizzy, Friesner, Daniel, Stastny, Sherri, Hackney, Kyle J, and Nawarathna, Dharmakeerthi.
"A Miniaturized MicroRNA Sensor Identifies Targets Associated with Weight Loss in a Diet and Exercise Intervention among Healthy Overweight Individuals". Sensors 22 (18). Country unknown/Code not available: MDPI. https://doi.org/10.3390/s22186758.https://par.nsf.gov/biblio/10396701.
@article{osti_10396701,
place = {Country unknown/Code not available},
title = {A Miniaturized MicroRNA Sensor Identifies Targets Associated with Weight Loss in a Diet and Exercise Intervention among Healthy Overweight Individuals},
url = {https://par.nsf.gov/biblio/10396701},
DOI = {10.3390/s22186758},
abstractNote = {Weight loss through dietary and exercise intervention is commonly prescribed but is not effective for all individuals. Recent studies have demonstrated that circulating microRNA (miR) biomarkers could potentially be used to identify individuals who will likely lose weight through diet and exercise and attain a healthy body weight. However, accurate detection of miRs in clinical samples is difficult, error-prone, and expensive. To address this issue, we recently developed iLluminate—a low-cost and highly sensitive miR sensor suitable for point-of-care testing. To investigate if miR testing and iLluminate can be used in real-world obesity applications, we developed a pilot diet and exercise intervention and utilized iLluminate to evaluate miR biomarkers. We evaluated the expression of miRs-140, -935, -let-7b, and -99a, which are biomarkers for fat loss, energy metabolism, and adipogenic differentiation. Responders lost more total mass, tissue mass, and fat mass than non-responders. miRs-140, -935, -let-7b, and -99a, collectively accounted for 6.9% and 8.8% of the explained variability in fat and lean mass, respectively. At the level of the individual coefficients, miRs-140 and -935 were significantly associated with fat loss. Collectively, miRs-140 and -935 provide an additional degree of predictive capability in body mass and fat mass alternations.},
journal = {Sensors},
volume = {22},
number = {18},
publisher = {MDPI},
author = {Jayasooriya, Vidura and Johnson, Nathaniel and Bradley, Adam and Kotarsky, Christopher and Jepng’etich, Lizzy and Friesner, Daniel and Stastny, Sherri and Hackney, Kyle J and Nawarathna, Dharmakeerthi},
}
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