**8. Conclusions**

While adipose tissue fibrosis has been investigated for several decades, there is still an incomplete understanding of causes, effects, and mechanisms. Under periods of high caloric consumption, the increase in adipocyte volume and tissue mass results in inflammation, metabolic dysregulation, and adipose tissue fibrosis in some individuals, but not all.

To address many of the open-ended questions surrounding adipose tissue fibrosis, in vitro and in vivo model systems should be carefully chosen to meet the needs of the research question. Three-dimensional in vitro models are an area of adipose tissue fibrosis research that has a high potential for growth. Improvements to this field would drastically enhance our understanding of the disease by creating physiologically relevant models where factors can be carefully manipulated, and treatments can be investigated in human samples. While using a biomaterial scaffold to model adipose tissue fibrosis would offer a high throughput, inexpensive disease model, the tradeoff is a lack of the complexities found in in vivo animal models, including systemic effects and immune responses [81]. Human epidemiological studies vary considerably depending on experimental setup and subject demographics. The effects of race, gender, and comorbidities have just begun to be investigated and

appear to have a significant effect on adipose tissue fibrosis [157–159]. More in-depth studies and integration of existing datasets [160] are needed to further investigate how patient demographics affect adipose tissue fibrosis.

Currently, there is also a large amount of research in treating other fibrotic diseases using cells and secreted vesicles from adipose tissue. As these treatments rely on cells functioning similarly in all patients the decreased ability to differentiate and exhibit a proinflammatory phenotype in fibrotic tissues is concerning.

Overall, adipose tissue fibrosis is not routinely screened for; however, it can have profound effects on patient outcomes and therapeutic options. With the rate of obesity increasing globally, it is essential that we develop a better understanding of fibrotic causes and mechanisms, as well as create better models to study potential treatments.

**Author Contributions:** Conceptualization, M.K.D. and R.D.A.; Literature Review, M.K.D. and R.D.A.; Figures and Tables, M.K.D.; Writing—Original Draft Preparation, M.K.D.; Writing—Review & Editing, R.D.A. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.
