Sławomir Grycel1, Adam R Markowski2, Hady Razak Hady3, Piotr Zabielski4, Iwona Kojta5, Monika Imierska5, Jan Górski6, Agnieszka U Blachnio-Zabielska7. 1. Specialist Medical Center "SOMED" Łomża, Poland. 2. Department of Internal Medicine and Gastroenterology, Polish Red Cross Memorial Municipal Hospital, Bialystok, Poland. 3. 1st Department of General Surgery and Endocrinology, Medical University Bialystok, Bialystok, Poland. 4. Department of Medical Biology, Medical University of Bialystok, Bialystok, Poland; Department of Physiology, Medical University of Bialystok, Bialystok, Poland. 5. Department of Hygiene, Epidemiology and Metabolic Disorders, Medical University of Bialystok, Bialystok, Poland. 6. Department of Physiology, Medical University of Bialystok, Bialystok, Poland; Department of Basic Sciences, Faculty of Health Sciences, Lomza State University of Applied Sciences, Lomza, Poland. 7. Department of Physiology, Medical University of Bialystok, Bialystok, Poland. Electronic address: Agnieszka.blachnio@umb.edu.pl.
Abstract
OBJECTIVES: Adipose tissue plays a central role in the pathogenesis of insulin resistance (IR) and type 2 diabetes. However, the molecular changes that promote these diseases are not completely understood. Several studies demonstrated that ceramide (Cer) and diacylglycerol (DAG) accumulation in muscle is associated with IR. The aim of this study was to explain whether a high-fat diet (HFD) leads to bioactive lipid accumulation in adipose tissue and how metformin affects the lipid content in adipocytes and the concentration of plasma adipocytokines. METHODS: The experiments were conducted on male Wistar rats divided into three groups: control, HFD-fed, and HFD-fed and treated with metformin. Cer and DAGs were analyzed by liquid chromatography tandem mass spectrometry. Phosphorylation of hormone-sensitive lipase (HSL) was analyzed by Western blot. Oral glucose tolerance and insulin tolerance tests were also performed. Plasma adiponectin and tumor necrosis factor (TNF)-α concentration were measured by enzyme-linked immunosorbent assay. RESULTS: HFD induced IR and elevated DAGs and Cer content in subcutaneous and visceral adipose tissues, which was accompanied by an increased phosphorylation of HSL. Metformin improved insulin sensitivity, decreased Cer and DAG levels, and attenuated the phosphorylation of HSL in both fat depots. Furthermore, we observed a strong correlation between adiponectin (negative) and TNF-α (positive) and bioactive lipids in both fat tissues. CONCLUSIONS: These results indicated that bioactive lipids accumulation in adipose tissue influences the induction of IR and, at least in part, answered the question of what the insulin-sensitizing effect of metformin at the level of adipose tissue is.
OBJECTIVES: Adipose tissue plays a central role in the pathogenesis of insulin resistance (IR) and type 2 diabetes. However, the molecular changes that promote these diseases are not completely understood. Several studies demonstrated that ceramide (Cer) and diacylglycerol (DAG) accumulation in muscle is associated with IR. The aim of this study was to explain whether a high-fat diet (HFD) leads to bioactive lipid accumulation in adipose tissue and how metformin affects the lipid content in adipocytes and the concentration of plasma adipocytokines. METHODS: The experiments were conducted on male Wistar rats divided into three groups: control, HFD-fed, and HFD-fed and treated with metformin. Cer and DAGs were analyzed by liquid chromatography tandem mass spectrometry. Phosphorylation of hormone-sensitive lipase (HSL) was analyzed by Western blot. Oral glucose tolerance and insulin tolerance tests were also performed. Plasma adiponectin and tumor necrosis factor (TNF)-α concentration were measured by enzyme-linked immunosorbent assay. RESULTS: HFD induced IR and elevated DAGs and Cer content in subcutaneous and visceral adipose tissues, which was accompanied by an increased phosphorylation of HSL. Metformin improved insulin sensitivity, decreased Cer and DAG levels, and attenuated the phosphorylation of HSL in both fat depots. Furthermore, we observed a strong correlation between adiponectin (negative) and TNF-α (positive) and bioactive lipids in both fat tissues. CONCLUSIONS: These results indicated that bioactive lipids accumulation in adipose tissue influences the induction of IR and, at least in part, answered the question of what the insulin-sensitizing effect of metformin at the level of adipose tissue is.