Effect of Different Dietary Fats on Gut Microbiota, Fatty Liver and Insulin Resistance in Postmenopausal Condition

Project: A - Government Institutionb - Ministry of Science and Technology

Description

Postmenopausal status is associated with higher prevalence of abdominal obesity, it caused by estrogen deficiency. Accumulating evidence indicates that abdominal obesity is closely associated with an increased risk of metabolic diseases such as type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). Altered gut microbiota (dysbiosis) may stimulate hepatic lipids deposition and cause metabolic disorders. Gut dysbiosis may alter epithelial tight junction, decrease GLP-1 and increase endotoxin secretion. Low GLP-1 level is associated with postmenopausal insulin resistance. Stimulation of the G protein coupled receptor (GPR)120 has been shown to have anti-inflammatory and insulin-sensitizing effects, to promote GLP-1 secretion, and to play a key role in sensing dietary fat and control energy balance. Studies also showed that GLP-1 can up-regulate peroxisome proliferators- activated receptor (PPAR)-γ expression to improve inflammatory diseases. PPAR-γ is expressed in adipose tissue, where it regulates adipocyte differentiation and inflammatory mediators. Besides, mitochondrial dysfunction is thought to play important roles in the pathogenesis of tissue injury result from estrogen deficiency. Proinflammatory cytokines and adipokines are dysregulation both in high fat diet-induced obesity (DIO) and postmenopausal condition. Ovariectomized (OVX) animal model is widely used in postmenopausal estrogen deficiency studies. Type of dietary fat influence the fatty acids profile in cell membrane and then affect the signaling pathway to regulate inflammatory response, hormone secretion and gene expression. Lard is rich in saturated fatty acid; a long-term consumption tends to cause insulin resistance. Olive oil (an import product) and tea seed oil (produced in Taiwan) are rich in monounsaturated fatty acids (MUFA). Soybean oil is rich in n-6 fatty acids; it is the largest amount of edible oil consumed in Taiwan. Besides, fish oil, rich in n-3 fatty acids, is able to reducing the level of proinflammatory cytokines and regulate lipid metabolism. Our preliminary experiments found that the n-3 fatty acids intervention may affect parts of mitochondria-related protein expression by proteomic analysis in OVX rat with NAFLD. However, few studies were performed the effect of different dietary fats on gut microbiota, NAFLD and insulin resistance in postmenopausal conditional. Therefore, this 3-year-study will be carried out to investigate the possible actions of dietary fats on gut microbiota, the role of GLP-1, the regulation of inflammatory mediators related with NAFLD and insulin resistance in postmenopausal condition. In the first year, we will treat OVX C57BL/6 mice with low high-fat diet to investigate the possible role of different dietary fats in gut microbiota, NAFLD, and insulin resistance. In the second year, we will treat OVX mice with a high-fat diet induced insulin resistance condition and then feed mice with different dietary fats to study the similar regulatory mechanisms like the first year in this postmenopausal model. A quantitative proteomic platform will use to explore the total and membrane protein expression of tissues in the 2nd and the 3rd years. Because our animal studies cannot directly explore the regulatory mechanism of adipocyte differentiation by which kind of fatty acids. Thus, in the third year we will cultivate 3T3-L1 (preadipocyte) different fatty acids under high concentration of glucose to mimic hyperglycemia. To investigate the regulatory effect of individual fatty acids on adipocyte differentiation, GLP-1 and PPAR-γ related pathway. The results of this proposal will lead to a better knowledge to understand the effect of different dietary fats on the gut microbiota, lipid metabolic regulatory mechanisms, insulin resistance and adipocyte differentiation in postmenopausal condition for nutritional applications.
StatusFinished
Effective start/end date8/1/167/31/17

Keywords

  • fatty acids
  • menopause
  • gut microbiota
  • insulin resistance
  • NAFLD
  • proteomic