Ankita Poojari

Bio: Ankita Poojari is an academic researcher from University of the Pacific (United States). The author has contributed to research in topics: Medicine & Induced pluripotent stem cell. The author has an hindex of 1, co-authored 1 publications receiving 3 citations.

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

Abstract: The concerning worldwide increase of obesity and chronic metabolic diseases, such as T2D, dyslipidemia, and cardiovascular disease, motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there has been growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat, as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Furthermore, we discuss the alterations in brown and beige adipose tissue function during obesity and explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

Neuropharmacology of human TERA2.cl.SP12 stem cell-derived neurons in ultra-long-term culture for antiseizure drug discovery

Abstract: Modeling the complex and prolonged development of the mammalian central nervous system in vitro remains a profound challenge. Most studies of human stem cell derived neurons are conducted over days to weeks and may or may not include glia. Here we have utilized a single human pluripotent stem cell line, TERA2.cl.SP12 to derive both neurons and glial cells and determined their differentiation and functional maturation over 1 year in culture together with their ability to display epileptiform activity in response to pro-convulsant agents and to detect antiseizure drug actions. Our experiments show that these human stem cells differentiate in vitro into mature neurons and glia cells and form inhibitory and excitatory synapses and integrated neural circuits over 6–8 months, paralleling early human neurogenesis in vivo; these neuroglia cultures display complex electrochemical signaling including high frequency trains of action potentials from single neurons, neural network bursts and highly synchronized, rhythmical firing patterns. Neural activity in our 2D neuron–glia circuits is modulated by a variety of voltage-gated and ligand-gated ion channel acting drugs and these actions were consistent in both young and highly mature neuron cultures. We also show for the first time that spontaneous and epileptiform activity is modulated by first, second and third generation antiseizure agents consistent with animal and human studies. Together, our observations strongly support the value of long-term human stem cell-derived neuroglial cultures in disease modeling and neuropsychiatric drug discovery.

Lipedema: Insights into Morphology, Pathophysiology, and Challenges

Abstract: Lipedema is an adipofascial disorder that almost exclusively affects women. Lipedema leads to chronic pain, swelling, and other discomforts due to the bilateral and asymmetrical expansion of subcutaneous adipose tissue. Although various distinctive morphological characteristics, such as the hyperproliferation of fat cells, fibrosis, and inflammation, have been characterized in the progression of lipedema, the mechanisms underlying these changes have not yet been fully investigated. In addition, it is challenging to reduce the excessive fat in lipedema patients using conventional weight-loss techniques, such as lifestyle (diet and exercise) changes, bariatric surgery, and pharmacological interventions. Therefore, lipedema patients also go through additional psychosocial distress in the absence of permanent treatment. Research to understand the pathology of lipedema is still in its infancy, but promising markers derived from exosome, cytokine, lipidomic, and metabolomic profiling studies suggest a condition distinct from obesity and lymphedema. Although genetics seems to be a substantial cause of lipedema, due to the small number of patients involved in such studies, the extrapolation of data at a broader scale is challenging. With the current lack of etiology-guided treatments for lipedema, the discovery of new promising biomarkers could provide potential solutions to combat this complex disease. This review aims to address the morphological phenotype of lipedema fat, as well as its unclear pathophysiology, with a primary emphasis on excessive interstitial fluid, extracellular matrix remodeling, and lymphatic and vasculature dysfunction. The potential mechanisms, genetic implications, and proposed biomarkers for lipedema are further discussed in detail. Finally, we mention the challenges related to lipedema and emphasize the prospects of technological interventions to benefit the lipedema community in the future.

The Stress Axis in Obesity and Diabetes Mellitus: An Update

Abstract: The hypothalamic–pituitary–adrenal axis is a tightly regulated system that represents one of the body’s mechanisms for responding to acute and chronic stress. Prolonged stress and/or inadequate regulation of the stress system can lead to a condition of chronic hypercortisolism or, in some cases, a blunted cortisol response to stress, contributing to insulin resistance, increased adiposity and type 2 diabetes mellitus. Moreover, acute and chronic stress can exacerbate or worsen metabolic conditions by supporting an inflammatory state and a tight relationship between stress, inflammation and adipose tissue has been reported and has been a growing subject of interest in recent years. We reviewed and summarized the evidence supporting hypothalamic–pituitary–adrenal axis dysregulation as an important biological link between stress, obesity, inflammation and type 2 diabetes mellitus. Furthermore, we emphasized the possible role of infectious-related stress such as SarsCov2 infection in adrenal axis dysregulation, insulin resistance and diabetes in a bidirectional link. Understanding and better defining the links between stress and obesity or diabetes could contribute to further definition of the pathogenesis and the management of stress-related complications, in which the HPA axis dysregulation has a primary role.

Crosstalk between adipose tissue and the microbiota-gut-brain axis in metabolic diseases

Abstract: Recently, the microbiota-gut-brain axis (MGBA) has emerged as a target for therapeutic innovation. Impairment of dynamic relationships within the MGBA promotes the pathological features of metabolic diseases. However, experimental data on the MGBA has limited clinical application. This review summarizes recent studies and proposes that exploring the interaction among peripheral organs and the MGBA could verify the dominant role of the latter in the onset of metabolic diseases and promote the clinical application of research outcomes. We first emphasize the molecular basis of metabolic diseases caused by MGBA disorders, which manifests as bidirectional relationship. We also summarize related therapeutic strategies, along with limitations in their clinical application. Adipose tissue (AT) is dynamic during metabolic activities and might interact with components in the MGBA. Therefore, it is interesting to explore the interplay among the MGBA and different kinds of AT, including thermogenic adipose tissue and white adipose tissue (WAT). In addition, we also evaluate the functional specificity of adipose tissue derived mesenchymal stem cells (ADSCs) and the beige adipose tissue. Understanding the heterogeneity and molecular basis of the interaction between different kinds of AT and the MGBA could accelerate innovation in the diagnosis and therapy of metabolic diseases.

Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis via intro-adipose sympathetic innervation

Abstract: Emerging evidence suggests that butyrate, a short-chain fatty acid, may have beneficial effects on obesity and its associated metabolic comorbidities, but the related molecular mechanism is largely unknown. This study aims to investigate the role of butyrate in diet-induced obesity and metabolic disorders and the relevant regulatory mechanisms. Here, dietary supplementation with Sodium butyrate (NaB) was carried out in mice fed with a high-fat diet (HFD) or chow diet. At week 14, mice on HFD displayed an obese phenotype and down-regulated expression of thermogenic regulators including Ucp-1 and Pgc-1α in adipose tissue. Excitingly, NaB add-on treatment abolished these detrimental effects. Moreover, the obesity-induced insulin resistance, inflammation, fatty liver, and intestinal dysfunction were also attenuated by NaB administration. Mechanistically, NaB can promote fat thermogenesis via the increased local sympathetic innervation of adipose tissue, and blocking the β3-adrenergic signaling pathway by 6-hydroxydopamine abolished NaB-induced thermogenesis. Our study reveals a potential pharmacological target for NaB to combat obesity and metabolic disorders.