Adipose Morphology: a Critical Factor in Regulation of Human Metabolic Diseases and Adipose Tissue Dysfunction

Abstract

Emerging evidence highlights that dysfunction of adipose tissue contributes to impaired insulin sensitivity and systemic metabolic deterioration in obese state. Of note, adipocyte hypertrophy serves as a critical event which associates closely with adipose dysfunction. An increase in cell size exacerbates hypoxia and inflammation as well as excessive collagen deposition, finally leading to metabolic dysregulation. Specific mechanisms of adipocyte hypertrophy include dysregulated differentiation and maturation of preadipocytes, enlargement of lipid droplets, and abnormal adipocyte osmolarity sensors. Also, weight loss therapies exert profound influence on adipocyte size. Here, we summarize the critical role of adipocyte hypertrophy in the development of metabolic disturbances. Future studies are required to establish a standard criterion of size measurement to better clarify the impact of adipocyte hypertrophy on changes in metabolic homeostasis.

Variables Associated with Short-Term Weight Loss in a Cohort of Patients with Morbid Obesity According to Age and Three Types of Bariatric Surgery

“…Other variables not considered in this study, such as the metabolic state of adipose tissue, could affect %EWL. The worse anthropometric characteristics of patients underwent BPD could alter the metabolism of adipose tissue: higher adipocyte hypertrophy is closely associated with a metabolic dysregulation [33], which could be associated with the evolution of these patients after BS [34]. On the other hand, and according to our results, there are studies showing a similar %EWL with RYGB [13,23].…”

The Role of Gut Microbiota and Its Produced Metabolites in Obesity, Dyslipidemia, Adipocyte Dysfunction, and Its Interventions

“…Healthy adipose tissue expansion is that of hyperplasia and adaptation; maintaining vascularization, increasing insulin sensitivity partly through adiponectin release, and allowing storage of triglycerides in a ‘healthy’ fashion, ready for release whenever energy is required [ 149 ]. However, in case of chronic overfeeding and obesity, adipose tissue does not only undergo physiologic hyperplasia, but it also hypertrophies [ 150 ]. Hypertrophic adipocytes do not store energy efficiently, but rather they are overloaded with triglycerides and excessively large cytoplasmic lipid droplets, and upon closer investigation, these enlarged adipocytes have inadequate vascularization, deteriorated mitochondrial oxygen use, hypoxia despite increased hypoxia-inducible factor 1-alpha (HIF1α), and as a result substantially increased reactive oxygen species (ROS) production, lipid peroxidation, and tissue fibrosis [ 149 , 150 , 151 , 152 ].…”

“…However, in case of chronic overfeeding and obesity, adipose tissue does not only undergo physiologic hyperplasia, but it also hypertrophies [ 150 ]. Hypertrophic adipocytes do not store energy efficiently, but rather they are overloaded with triglycerides and excessively large cytoplasmic lipid droplets, and upon closer investigation, these enlarged adipocytes have inadequate vascularization, deteriorated mitochondrial oxygen use, hypoxia despite increased hypoxia-inducible factor 1-alpha (HIF1α), and as a result substantially increased reactive oxygen species (ROS) production, lipid peroxidation, and tissue fibrosis [ 149 , 150 , 151 , 152 ]. Hypertrophic adipose tissue does not allow for normal adipogenesis.…”

Association of Omental Adipocyte Hypertrophy and Fibrosis with Human Obesity and Type 2 Diabetes

“…After insulin stimulation, the amount of glucose transporter type 4 (GLUT4) in the plasma membrane of large adipocytes did not increase, although there was a twofold increase in small cells (25), indicating abnormal glucose metabolism in enlarged adipocytes. Also, the function of insulin in inhibiting lipolysis was weakened, and hypertrophic adipocytes showed an increased basal rate of lipolysis and the following unesterified fatty acid and cholesterol overflow to skeletal muscles and liver (6). In this context, we found T2DM patients displayed larger adipocytes than the OB and NGT patients.…”

“…Overgrowth of adipocyte size, termed “adipocyte hypertrophy,” exacerbates tissue hypoxia, which further causes systemic lipid overload and ectopic fat deposition in peripheral organs and leads to systemic insulin resistance (4), a direct morphological manifestation to predict adipose tissue dysfunction. In obesity, visceral adipocyte size increases with weight gain and positively associates with impairment of insulin sensitivity (5,6). Generally, adipocyte hypertrophy has been regarded as an important feature of the obese state.…”