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Insulin resistance and high TNFα concentrations precede obesity in rats fed high carbohydrate diet during suckling period
S186
Poster Session 1
This study shows that Indians have higher triglycerides (Ind 1.2f0.4 mmol/L, Chi 0.8f0.3, Cau 0.8f0.3; p=O.Ol, ANOVA), fasting insulin (Ind 7.8f3.0 ng/mL, Chi 5.4f2.9, Cau 4.2f1.4; p=O.Ol), leptin (Ind 5.1f2.5 ng/mL, Chi l.lfl.O, Cau 2.3fl.2; p
I’727 Insulin Signal ‘lkansduction and Glucose ‘lkansport in Adipocytes from Obese Women: Effects of Low Calorie Diet MARIE BJGRNHOLM’, Lubna Al-Khalili’, Anna Krook’, Stephan RGssnerZ, Juleen R. Zierath’, Peter Amer*. ’ Clinical Physiology at Karolinska Hospital, Karolinska Institute, Stockholm, Sweden; 2 Obesity Unit at Huaiiinge Hospital, Medicine and Research Center at Huddinge Hospital, Karolinska Institute, Stockholm, Sweden
Aim: We examined the effects of caloric restriction on insulin signal transduction and glucose transport in isolated adipocytes from obese women. Methods: Six obese, but otherwise healthy women (29-56 years; BMI 36.2-43.1 kg/m2) were studied before and after 8-16 days of very low calorie diet (VLCD). Weight loss ranged from 2.4-7.2 kg. Six lean women (BMI 21.7-25.7 kg/m2) on an isocaloric diet served as controls. A subcutaneous adipose tissue biopsy was taken from the abdominal area under local anesthesia. Isolated adipocytes were prepared and incubated in vitro without or with insulin (3 or 1000 nM) for 10 min. Results: Insulinstimulated glucose transport in isolated adipocytes was reduced 20% in obese women (p
F728 Insulin Resistance of Human Adipose Tissue in Obesity Measured with [lsF]FDG and PET KIRSI A. VIRTANEN ’ , Pauliina Peltoniemi ’ , P&i Marjamaki ’ , Markku Asola ’ , Riitta Parkkola4, Risto Huupponen 3, Peter Liinnroth’, Tapani RGnnemaa5, Juhani Knuuti ‘, Pirjo Nuutila’. ’ Turku PET Centre, University of Turku, Turku, Finland; 2 Dept. of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden: 3 Dept. of Pharmacology and Clinical Pharmacology, University of Turku; ‘Dept. of Radiology, 5 Dept. of Internal Medicine, Turku University Central Hospital, Turku, Finland
The metabolic significance of various adipose tissue depots has not previously been directly measured in vivo. In the present study we compared insulin-stimulated glucose uptake rates in subcutaneous (SAT) and visceral adipose tissue (VAT) in non-obese and obese subjects. Ten obese (BMI 30f2 kg/m*) and ten non-obese (BMI 22fl kg/m*) age-matched men were studied under euglycemic hyperinsulinemic clamp conditions (1 mU/kgmin.). Adipose tissue and skeletal muscle glucose uptake were measured using [tsF]fluoro-2-deoxy-D-glucose ([‘sF]FDG) and positron emission tomography (PET). Lumped constant value of 1.2 was used for [“F]FDG as measured recently with microdialysis and [‘50]Hs0. Magnetic resonance images were used as reference to PET for adipose tissue localization. The obese subjects exhibited resistance to insulin stimulation of glucose uptake in the skeletal muscles (25f5 vs 42f4 bmol/kg musclemin., ~~0.05, obese vs. non-obese), in abdominal SAT (5.8f0.7 vs 19.8f4.2 wmobkg SAT.min, p
I’729 Insulin Resistance and High TNFar Concentrations Precede Obesity in Rats Fed High Carbohydrate Diet during Suckling Period HUSAM GHANIM, Malathi Srinivisan, Ravikumar Aalinkeel, Mulchand S. Patel, Paresh Dandona. Diabetes-Endocrinology Center of Western New York, Kaleida Health and State University of New York, Buffalo, NX United States of America
Obesity is a major risk factor for non-insulin dependent diabetes mellitus (NIDDM) and is associated with insulin resistance. Tumor necrosis factor-alpha (TNFo) has been found to be over-expressed in several rodent models of obesity and diabetes, as well as in obese humans and may be linked to the development of insulin resistance. In this study, we examined a rat model of obesity, which is developed by feeding neonatal rat pups with an isocaloric diet high in carbohydrates (HC) during the suckling period (day 4 to 24) compared to naturally reared pups on mother’s milk @IF). The HC adult rats became hyperinsulinemic with normoglycemia on day 5 and obese at day 60. We measured TNFo and leptin concentrations during the suckling period (day 12) and in 1 year old rats. TNFo concentrations were higher at day 12 in pups from the HC group, compared to the MF group (0.695 + 0.142 vs 0.508 f 0.175 pg/mL) (p-zO.OOl), while leptin concentrations were not significantly different at this stage (1545.5 f 1060.7 pg/mL in HC vs. 1801.0 f 1302.8 pg/mL in MF). In 1 year old rats, TNFo and leptin plasma concentrations were also higher in the HC group compared to the MF group (5.477 + 1.827 vs. 4.035 f 0.991 pg/mL, ~~0.05 and 32183.5 * 22413.5 vs. 4969.8 f 3708.2 pg/mL, ~~0.05 respectively). Also total cell lysate of the epididymal adipose tissue showed 2.5 fold higher in TNFo in HC, when compared to that from MF (p=O.OOl). We conclude that the isocaloric feeding of HC milk during the suckling period is associated with obesity later in life, but that hyperinsulinemiaand the increase in TNFa occur early, while the increase in leptin occurs in association with obesity much later.
Poster Session 1
This study shows that Indians have higher triglycerides (Ind 1.2f0.4 mmol/L, Chi 0.8f0.3, Cau 0.8f0.3; p=O.Ol, ANOVA), fasting insulin (Ind 7.8f3.0 ng/mL, Chi 5.4f2.9, Cau 4.2f1.4; p=O.Ol), leptin (Ind 5.1f2.5 ng/mL, Chi l.lfl.O, Cau 2.3fl.2; p
I’727 Insulin Signal ‘lkansduction and Glucose ‘lkansport in Adipocytes from Obese Women: Effects of Low Calorie Diet MARIE BJGRNHOLM’, Lubna Al-Khalili’, Anna Krook’, Stephan RGssnerZ, Juleen R. Zierath’, Peter Amer*. ’ Clinical Physiology at Karolinska Hospital, Karolinska Institute, Stockholm, Sweden; 2 Obesity Unit at Huaiiinge Hospital, Medicine and Research Center at Huddinge Hospital, Karolinska Institute, Stockholm, Sweden
Aim: We examined the effects of caloric restriction on insulin signal transduction and glucose transport in isolated adipocytes from obese women. Methods: Six obese, but otherwise healthy women (29-56 years; BMI 36.2-43.1 kg/m2) were studied before and after 8-16 days of very low calorie diet (VLCD). Weight loss ranged from 2.4-7.2 kg. Six lean women (BMI 21.7-25.7 kg/m2) on an isocaloric diet served as controls. A subcutaneous adipose tissue biopsy was taken from the abdominal area under local anesthesia. Isolated adipocytes were prepared and incubated in vitro without or with insulin (3 or 1000 nM) for 10 min. Results: Insulinstimulated glucose transport in isolated adipocytes was reduced 20% in obese women (p
F728 Insulin Resistance of Human Adipose Tissue in Obesity Measured with [lsF]FDG and PET KIRSI A. VIRTANEN ’ , Pauliina Peltoniemi ’ , P&i Marjamaki ’ , Markku Asola ’ , Riitta Parkkola4, Risto Huupponen 3, Peter Liinnroth’, Tapani RGnnemaa5, Juhani Knuuti ‘, Pirjo Nuutila’. ’ Turku PET Centre, University of Turku, Turku, Finland; 2 Dept. of Internal Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden: 3 Dept. of Pharmacology and Clinical Pharmacology, University of Turku; ‘Dept. of Radiology, 5 Dept. of Internal Medicine, Turku University Central Hospital, Turku, Finland
The metabolic significance of various adipose tissue depots has not previously been directly measured in vivo. In the present study we compared insulin-stimulated glucose uptake rates in subcutaneous (SAT) and visceral adipose tissue (VAT) in non-obese and obese subjects. Ten obese (BMI 30f2 kg/m*) and ten non-obese (BMI 22fl kg/m*) age-matched men were studied under euglycemic hyperinsulinemic clamp conditions (1 mU/kgmin.). Adipose tissue and skeletal muscle glucose uptake were measured using [tsF]fluoro-2-deoxy-D-glucose ([‘sF]FDG) and positron emission tomography (PET). Lumped constant value of 1.2 was used for [“F]FDG as measured recently with microdialysis and [‘50]Hs0. Magnetic resonance images were used as reference to PET for adipose tissue localization. The obese subjects exhibited resistance to insulin stimulation of glucose uptake in the skeletal muscles (25f5 vs 42f4 bmol/kg musclemin., ~~0.05, obese vs. non-obese), in abdominal SAT (5.8f0.7 vs 19.8f4.2 wmobkg SAT.min, p
I’729 Insulin Resistance and High TNFar Concentrations Precede Obesity in Rats Fed High Carbohydrate Diet during Suckling Period HUSAM GHANIM, Malathi Srinivisan, Ravikumar Aalinkeel, Mulchand S. Patel, Paresh Dandona. Diabetes-Endocrinology Center of Western New York, Kaleida Health and State University of New York, Buffalo, NX United States of America
Obesity is a major risk factor for non-insulin dependent diabetes mellitus (NIDDM) and is associated with insulin resistance. Tumor necrosis factor-alpha (TNFo) has been found to be over-expressed in several rodent models of obesity and diabetes, as well as in obese humans and may be linked to the development of insulin resistance. In this study, we examined a rat model of obesity, which is developed by feeding neonatal rat pups with an isocaloric diet high in carbohydrates (HC) during the suckling period (day 4 to 24) compared to naturally reared pups on mother’s milk @IF). The HC adult rats became hyperinsulinemic with normoglycemia on day 5 and obese at day 60. We measured TNFo and leptin concentrations during the suckling period (day 12) and in 1 year old rats. TNFo concentrations were higher at day 12 in pups from the HC group, compared to the MF group (0.695 + 0.142 vs 0.508 f 0.175 pg/mL) (p-zO.OOl), while leptin concentrations were not significantly different at this stage (1545.5 f 1060.7 pg/mL in HC vs. 1801.0 f 1302.8 pg/mL in MF). In 1 year old rats, TNFo and leptin plasma concentrations were also higher in the HC group compared to the MF group (5.477 + 1.827 vs. 4.035 f 0.991 pg/mL, ~~0.05 and 32183.5 * 22413.5 vs. 4969.8 f 3708.2 pg/mL, ~~0.05 respectively). Also total cell lysate of the epididymal adipose tissue showed 2.5 fold higher in TNFo in HC, when compared to that from MF (p=O.OOl). We conclude that the isocaloric feeding of HC milk during the suckling period is associated with obesity later in life, but that hyperinsulinemiaand the increase in TNFa occur early, while the increase in leptin occurs in association with obesity much later.