Impact of human visceral and glutealfemoral adipose tissue transplant on glycemic control in a mouse model of diet-induced obesity.

Regional distribution of adipose tissue is an important factor in conferring cardiometabolic risk and obesity-related morbidity. We tested the hypothesis that human visceral adipose tissue (VAT) impairs glucose homeostasis, whereas subcutaneous glutealfemoral adipose tissue (GFAT) protects against the development of impaired glucose homeostasis in mice. VAT and GFAT were collected from patients undergoing bariatric surgery and grafted onto the epididymal adipose tissue of weight- and age-matched severe, combined immunodeficient mice. SHAM mice underwent surgery without transplant of tissue. Mice were fed a high-fat diet after xenograft. Energy homeostasis, glucose metabolism, and insulin sensitivity were assessed 6 wk later. Xenograft of human adipose tissues was successful, as determined by histology, immunohistochemical evaluation of collagen deposition and angiogenesis, and maintenance of lipolytic function. Adipose tissue transplant did not affect energy expenditure, food intake, whole body substrate partitioning, or plasma free fatty acid, triglyceride, and insulin levels. Fasting blood glucose was significantly reduced in GFAT and VAT compared with SHAM, whereas glucose tolerance was improved only in mice transplanted with VAT compared with SHAM mice. This improvement was not associated with differences in whole body insulin sensitivity or plasma insulin between groups. Together, these data suggest that VAT improves glycemic control and GFAT does not protect against the development of high-fat diet-induced glucose intolerance. Hence, the intrinsic properties of VAT and GFAT do not necessarily explain the postulated negative and positive effects of these adipose tissue depots on metabolic health.

Impact of endurance exercise training on adipocyte microRNA expression in overweight men.

Adipocytes are major regulators of metabolism, and endurance exercise training improves adipocyte function; however, the molecular mechanisms that regulate chronic adaptive responses remain unresolved. microRNAs (miRNAs) influence adipocyte differentiation and metabolism. Accordingly, we aimed to determine whether adipocyte miRNA expression is responsive to exercise training and to identify exercise-responsive miRNAs that influence adipocyte metabolism. Next-generation sequencing was used to profile miRNA expression of adipocytes that were isolated from abdominal subcutaneous (ABD) and gluteofemoral (GF) adipose tissue of overweight men before and after 6 wk of endurance exercise training. Differentially expressed miRNAs were overexpressed or silenced in 3T3-L1 adipocytes, and lipid metabolism was examined. Next-generation sequencing identified 526 miRNAs in adipocytes, and there were no statistical differences in miRNA expression when comparing pre- and post-training samples for ABD and GF adipocytes. miR-10b expression was increased in ABD compared with GF adipocytes, whereas miR-204, miR-3613, and miR-4532 were more highly expressed in GF compared with ABD adipocytes. Blocking miR-10b in adipocytes suppressed ß-adrenergic lipolysis but generally had a minor effect on lipid metabolism. Thus, unlike their critical role in adipogenesis, stable changes in miRNA expression do not play a prominent role in the regulation of adipocyte function in response to endurance exercise training.-Tsiloulis, T., Pike, J., Powell, D., Rossello, F. J., Canny, B. J., Meex, R. C. R., Watt, M. J. Impact of endurance exercise training on adipocyte microRNA expression in overweight men.

Adipose tissue development and the molecular regulation of lipid metabolism.

The production of new adipocytes is required to maintain adipose tissue mass and involves the proliferation and differentiation of adipocyte precursor cells (APCs). In this review, we outline new developments in understanding the phenotype of APCs and provide evidence suggesting that APCs differ between distinct adipose tissue depots and are affected by obesity. Post-mitotic mature adipocytes regulate systemic lipid homeostasis by storing and releasing free fatty acids, and also modulate energy balance via the secretion of adipokines. The review highlights recent advances in understanding the cellular and molecular mechanisms regulating adipocyte metabolism, with a particular focus on lipolysis regulation and the involvement of microribonucleic acids (miRNAs).

Exercise and the Regulation of Adipose Tissue Metabolism.

Adipose tissue is a major regulator of metabolism in health and disease. The prominent roles of adipose tissue are to sequester fatty acids in times of energy excess and to release fatty acids via the process of lipolysis during times of high-energy demand, such as exercise. The fatty acids released during lipolysis are utilized by skeletal muscle to produce adenosine triphosphate to prevent fatigue during prolonged exercise. Lipolysis is controlled by a complex interplay between neuro-humoral regulators, intracellular signaling networks, phosphorylation events involving protein kinase A, translocation of proteins within the cell, and protein-protein interactions. Herein, we describe in detail the cellular and molecular regulation of lipolysis and how these processes are altered by acute exercise. We also explore the processes that underpin adipocyte adaptation to endurance exercise training, with particular focus on epigenetic modifications, control by microRNAs and mitochondrial adaptations. Finally, we examine recent literature describing how exercise might influence the conversion of traditional white adipose tissue to high energy-consuming "brown-like" adipocytes and the implications that this has on whole-body energy balance.