Obesity, Type 2 Diabetes, and metabolic stress are systemic health issues that result from dysfunctions of white adipose tissue (WAT). As an endocrine organ, WAT is often possessed of a high degree of plasticity, capable of matching the metabolic conditions of which it is presented and responsible for maintaining an overall homeostatic energy balance. However, a clearer understanding of this expansile capacity, the cellular interactions within the tissue, and the mechanisms that drive deleterious pathophysiology remains to be elucidated. Many players are involved in these processes, but the focus of this dissertation centered around G-protein pathway suppressor 2 (GPS2), a protein with well-characterized connections to adipocytes, adipose stromal cells, and the maintenance of metabolism in response to dietary stress. Previous in vivo work showed that selective loss of GPS2 under high-fat diet (HFD) conditions leads to a Type 2 Diabetic-like phenotype. Here, through the implementation of this same adipocyte-specific GPS2 knockout mouse model, we have demonstrated that insulin resistance, inflammation, and unhealthy adipose tissue expansion arises within the first few weeks of exposure to a high-fat diet. In addition, characterization of the heterogeneous cellular milieu that exists within WAT via single-cell RNA sequencing and flow cytometric analyses identified changes in the non-immune adipocyte progenitor populations, along with immune macrophage subsets, the likes of which collectively contribute to adipose tissue remodeling in response to dietary challenge, and are impacted by the loss of GPS2 in the adipocytes. Insights into the mechanisms of cellular communication that are driving the observed cell-specific changes and whole-body mouse phenotype were provided via bulk RNA sequencing of the GPS2-null adipocytes following an acute HFD challenge, whereby we observed transcriptional signatures related to secretion of factors related to inflammation, tissue remodeling, and communication via exosomes. By additionally profiling adipocyte-secreted exosomes via semi-quantitative mass spectrometry, we were able outline specific connections between adipocytes and cell types found within the adipose stroma, along with GPS2-dependent, functionally consequential changes in exosomal cargo related to pro-fibrotic and anti-adipogenic proteins (processes that are critical in healthy adipose tissue expansion). Collectively, our data reveal that the selective loss of GPS2 in adipocytes impairs the reprogramming of adipose-derived signaling to other cells within the stroma in response to HFD, with this impairment mediated by exosomal cargo that has a local functional impact on both immune and non-immune cell types, and global impact on whole-body adipose tissue dysfunction. / 2024-11-02T00:00:00Z

The upcoming Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) will change how Alcohol Use Disorder (AUD) is characterized by going from a twoactor hierarchical model to a unidimensional disorder. In addition, the number of criteria needed are being reduced—which may increase AUD prevalence rates. The present study examines how these changes will impact college students as compared to their non-college attending peers. Participants were asked to complete questionnaires about their alcohol use and what criteria they meet, a daily functioning questionnaire, and a measure to determine their willingness to engage in risky behaviors. Results indicate that college students will show a disproportionate increase in diagnoses, even though college students who meet criteria show no significant differences in functional impairment compared to students who do not meet criteria. These results suggest that the new criteria may not be a good indicator of AUD presence for college students.

No description available.

No description available.

Thesis--K obenhavns universitet. / Bibliography: p. [122]-124.

Thesis--K obenhavns universitet. / Bibliography: p. [122]-124.

Akademisk avhandling--Arkeologi--Lund, 1980. / Bibliogr. p. 232-236.

Proefschrift--Leiden. / "Summary of results" in English.

Proefschrift--Leyden. / With summaries in English and Indonesian.

Proefschrift - Utrecht. / Summary in Dutch and English.