ICAM-1 and beta2 integrin deficiency impairs fat oxidation and insulin metabolism during fasting.
نویسندگان
چکیده
Intercellular adhesion molecule 1 (ICAM-1) and beta2 integrins play critical roles in immune responses. ICAM-1 may also participate in regulation of energy balance because ICAM-1-deficient mice become obese on a high-fat diet. We show that mice deficient in these adhesion receptors are unable to respond to fasting by up-regulation of fatty acid oxidation. Normal mice, when fasted, exhibit reduced circulating neutrophil counts and increased ICAM-1 expression and neutrophil recruitment in liver. Mice lacking ICAM-1 or beta2 integrins fail to show these responses--instead they become hypoglycemic with steatotic livers. Fasting ICAM-1-deficient mice reduce insulin more slowly than wild-type mice. This produces fasting hyperinsulinemia that prevents activation of adenosine mono-phosphate (AMP)-activated protein kinase in muscles and liver, which results in decreased import of long chain fatty acids into mitochondria. Thus, we show a new role for immune cells and their adhesion receptors in regulating metabolic response to fasting.
منابع مشابه
Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss.
The current study was undertaken to investigate fatty acid metabolism by skeletal muscle to examine potential mechanisms that could lead to increased muscle triglyceride in obesity. Sixteen lean and 40 obese research volunteers had leg balance measurement of glucose and free fatty acid (FFA) uptake (fractional extraction of [9,103H]oleate) and indirect calorimetry across the leg to determine su...
متن کاملA novel leukocyte adhesion deficiency caused by expressed but nonfunctional beta2 integrins Mac-1 and LFA-1.
In the leukocyte adhesion deficiency (LAD)-1 syndrome, there is diminished expression of beta2(CD18) integrins. This is caused by lesions in the beta2-subunit gene and gives rise to recurrent bacterial infections, impaired pus formation, and poor wound healing. We describe a patient with clinical features compatible with a moderately severe phenotype of LAD-1 but who expresses the beta2 integri...
متن کاملEffects of vitamin D supplementation and resistance training on insulin resistance, lipid profile and body fat percentage in T2D men with vitamin D deficiency.
Background and Aim: The aim of this study was to investigate the effects of vitamin D supplementation during progressive resistance training on insulin resistance, blood lipids and body fat percentage in T2D men with vitamin D deficiency. Methods: Forty-eight men with T2D participated in the study voluntarily and were randomly assigned to 4 groups (n=12) including, resistance training (RT), vi...
متن کاملProgressive adaptation of hepatic ketogenesis in mice fed a high-fat diet.
Hepatic ketogenesis provides a vital systemic fuel during fasting because ketone bodies are oxidized by most peripheral tissues and, unlike glucose, can be synthesized from fatty acids via mitochondrial beta-oxidation. Since dysfunctional mitochondrial fat oxidation may be a cofactor in insulin-resistant tissue, the objective of this study was to determine whether diet-induced insulin resistanc...
متن کاملEnhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity.
Skeletal muscle insulin resistance entails dysregulation of both glucose and fatty acid metabolism. This study examined whether a combined intervention of physical activity and weight loss influences fasting rates of fat oxidation and insulin-stimulated glucose disposal. Obese (BMI >30 kg/m(2)) volunteers (9 men and 16 women) without diabetes, aged 39 +/- 4 years, completed 16 weeks of moderate...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Molecular medicine
دوره 10 7-12 شماره
صفحات -
تاریخ انتشار 2004