Olga T. Gupta

Activated Kupffer cells inhibit insulin sensitivity in obese mice

Obesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although insulin resistance is attenuated in genetic mouse models that suppress systemic inflammation, it is not clear whether local resident macrophages in liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed this question by selectively silencing the expression of the master regulator of inflammation, NF‐κB, in KCs in obese mice. We used glucan‐encapsulated small interfering RNA particles (GeRPs) that selectively silence gene expression in macrophages in vivo. Following intravenous injections, G‐eRPs containing siRNA against p65 of the NF‐κB complex caused loss of NF‐κB p65 expression in KCs without disrupting NF‐κB in hepatocytes or macrophages in other tissues. Silencing of NF‐κB expression in KCs in obese mice decreased cytokine secretion and improved insulin sensitivity and glucose tolerance without affecting hepatic lipid accumulation. Importantly, GeRPs had no detectable toxic effect. Thus, KCs are key contributors to hepatic insulin resistance in obesity and a potential therapeutic target for metabolic disease.—Tencerova, M., Aouadi, M., Vangala, P., Nicoloro, S. M., Yawe, J. C., Cohen, J. L., Shen, Y., Garcia‐Menendez, L., Pedersen, D. J., Gallagher‐Dorval, K., Perugini, R. A., Gupta, O. T., Czech, M. P. Activated Kupffer cells inhibit insulin sensitivity in obese mice. FASEB J. 29, 2959‐2969 (2015). www.fasebj.org

Engaging Teens and Parents in Collaborative Practice: Perspectives on Diabetes Self-Management

Purpose The purpose of this exploratory focus group study was to describe the perspectives of teens and their parents about self-management knowledge, behaviors (including division of labor associated with T1D management), and resources used to manage T1D. The overall goal is to use this information to develop a teen–family transition clinic. Methods The self and family management behaviors framework undergirded the separate teen–parent focus groups that were conducted concurrently. Note-based qualitative content analysis was used, resulting in several important messages. Results From the teens’ perspective there was variation in interest in learning more about T1D and management. Those teens who had been diagnosed at a very young age reported not knowing anything else but diabetes, while those diagnosed later developmentally embraced the active learning process. Diabetes camp and peer group support were not seen as beneficial. All the teens were interested in “helping others” with diabetes. Parents shared the common struggle with transition of self-management, with variation in parenting styles. A small group of parents reported their “job” as a parent was to make sure their child was self-sufficient in self-management, but felt pressure from the health care providers (HCPs) to physically do the care, defeating the purpose. Parents and teens reported wanting HCPs to be less focused on “numbers” (blood glucose levels) and more on the whole person. Scheduling appointment changes and long waiting times were reported as problematic by all participants. Conclusions Teen and parent perspectives are critical in designing future well-received adolescent–family transition clinics. Development from the ground up with family recommendations may contribute to high-quality health outcomes.

Association between Responsible Pet Ownership and Glycemic Control in Youths with Type 1 Diabetes

Type 1 diabetes mellitus (T1DM) a chronic characterized by an absolute insulin deficiency requires conscientious patient self-management to maintain glucose control within a normal range. Family cohesion and adaptability, positive coping strategies, social support and adequate self-regulatory behavior are found to favorably influence glycemic control. Our hypothesis was that the responsible care of a companion animal is associated with these positive attributes and correlated with the successful management of a chronic illness such as type 1 diabetes. We recruited 223 youths between 9 and 19 years of age from the Pediatric Diabetes clinic at the University of Massachusetts Medical School, reviewed the status of their glycemic control (using three consecutive A1c values) and asked them questions about the presence of a pet at home, and their level of involvement with its care. Multivariate analyses show that children who care actively for one or more pets at home are 2.5 times more likely to have control over their glycemic levels than children who do not care for a pet, adjusting for duration of disease, socio-economic status, age and self-management [1.1 to 5.8], pWald = 0.032. A separate model involving the care of a petdog only yielded comparable results (ORa = 2.6 [1.1 to 5.9], pWald = 0.023).

Adipocyte-specific Hypoxia-inducible gene 2 promotes fat deposition and diet-induced insulin resistance

Objective Adipose tissue relies on lipid droplet (LD) proteins in its role as a lipid-storing endocrine organ that controls whole body metabolism. Hypoxia-inducible Gene 2 (Hig2) is a recently identified LD-associated protein in hepatocytes that promotes hepatic lipid storage, but its role in the adipocyte had not been investigated. Here we tested the hypothesis that Hig2 localization to LDs in adipocytes promotes adipose tissue lipid deposition and systemic glucose homeostasis. Method White and brown adipocyte-deficient (Hig2fl/fl × Adiponection cre+) and selective brown/beige adipocyte-deficient (Hig2fl/fl × Ucp1 cre+) mice were generated to investigate the role of Hig2 in adipose depots. Additionally, we used multiple housing temperatures to investigate the role of active brown/beige adipocytes in this process. Results Hig2 localized to LDs in SGBS cells, a human adipocyte cell strain. Mice with adipocyte-specific Hig2 deficiency in all adipose depots demonstrated reduced visceral adipose tissue weight and increased glucose tolerance. This metabolic effect could be attributed to brown/beige adipocyte-specific Hig2 deficiency since Hig2fl/fl × Ucp1 cre+ mice displayed the same phenotype. Furthermore, when adipocyte-deficient Hig2 mice were moved to thermoneutral conditions in which non-shivering thermogenesis is deactivated, these improvements were abrogated and glucose intolerance ensued. Adipocyte-specific Hig2 deficient animals displayed no detectable changes in adipocyte lipolysis or energy expenditure, suggesting that Hig2 may not mediate these metabolic effects by restraining lipolysis in adipocytes. Conclusions We conclude that Hig2 localizes to LDs in adipocytes, promoting adipose tissue lipid deposition and that its selective deficiency in active brown/beige adipose tissue mediates improved glucose tolerance at 23 °C. Reversal of this phenotype at thermoneutrality in the absence of detectable changes in energy expenditure, adipose mass, or liver triglyceride suggests that Hig2 deficiency triggers a deleterious endocrine or neuroendocrine pathway emanating from brown/beige fat cells.

A novel behavioral intervention in adolescents with type 1 diabetes mellitus improves glycemic control: preliminary results from a pilot randomized control trial.

Purpose The purpose of this study was to develop and pilot-test an innovative behavioral intervention in adolescents with type 1 diabetes mellitus (T1DM) incorporating structured care of a pet to improve glycemic control. Methods Twenty-eight adolescents with A1C > 8.5% (69 mmol/mol) were randomly assigned to either the intervention group (care of a Betta splendens pet fish) or the control group (usual care). Adolescents in the intervention group were given instructions to associate daily and weekly fish care duties with diabetes self-management tasks, including blood glucose testing and parent-adolescent communication. Results After 3 months, the participants in the intervention group exhibited a statistically significant decrease in A1C level (−0.5%) compared with their peers in the control group, who had an increase in A1C level (0.8%) (P = .04). The younger adolescents (10-13 years of age) demonstrated a greater response to the intervention, which was statistically significant (−1.5% vs 0.6%, P = .04), compared with the older adolescents (14-17 years of age). Conclusions Structured care of a pet fish can improve glycemic control in adolescents with T1DM, likely by providing cues to perform diabetes self-management behaviors.

Visceral Adipose Tissue Mesothelial Cells: Living on the Edge or Just Taking Up Space?

Visceral adiposity and pathological adipose tissue remodeling, a result of overnutrition, are strong predictors of metabolic health in obesity. Factors intrinsic to visceral adipose depots are likely to play a causal role in eliciting the detrimental effects of this tissue on systemic nutrient homeostasis. The visceral adipose-associated mesothelium, a monolayer of epithelial cells of mesodermal origin that line the visceral serosa, has recently attracted attention for its role in metabolic dysfunction. Here we highlight and consolidate literature from various fields of study that points to the visceral adipose-associated mesothelium as a potential contributor to adipose development and remodeling. We propose a hypothesis in which adipose mesothelial cells represent a visceral depot-specific determinant of adipose tissue health in obesity.

Camp-based multi-component intervention for families of young children with type 1 diabetes: A pilot and feasibility study

Managing type 1 diabetes mellitus (T1DM) in preschool‐aged children has unique challenges that can negatively impact glycemic control and parental coping.

Improving medication adherence in the pediatric population using integrated care of companion animals

Medication non-adherence occurs in more than half of children with chronic conditions. Unfortunately, most strategies for improving adherence have had limited success in the pediatric population highlighting the need for novel interventions that establish healthy self-management habits for children and adolescents. In this paper we discuss innovative strategies to improve adherence by embedding a medical regimen within a pet care routine, thereby capitalizing on the benefits of a structured habit while providing opportunities for development of autonomy in children and fostering collaborative parent interactions.