scholarly journals The metabolic syndrome of fructose-fed rats: Effects of long-chain polyunsaturated ω3 and ω6 fatty acids. I. Intraperitoneal glucose tolerance test

Author(s):  
Willy J. Malaisse
2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1243-1243
Author(s):  
Pascal Rowart ◽  
Sonia Salvatore ◽  
Fei Chang ◽  
Nicholas Khoo ◽  
Francisco Schopfer

Abstract Objectives Obesity and non-alcoholic fatty liver diseases (NAFLD) are multifactorial diseases that affect more than 35% of the world's population. Fish oil (FO) is an important dietary component that provides essential omega-3 fatty acids (Ω-3) effective for hypertriglyceridemia with eicosapentaenoic acid shown to reduce cardiovascular and metabolic syndrome-related events. However, the mechanisms involved in these beneficial activities are still unclear. A metabolomic study of healthy volunteers receiving Lovaza, an omega-3-drug, showed a large increase in plasma and urinary metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF). Moreover, in the diet-induced obesity (DIO) mouse model, CMPF was protective and reversed steatosis. We identified furan fatty acids (FuFA) present both in FO and Lovaza (0.1–1%) as the sources of CMPF and hypothesised that they were responsible for these beneficial effects. Methods We synthesized one FuFA and confirmed its structure by NMR and mass spectrometry and tested whether it had protective effects in this DIO model (23 weeks, 60 kcal% fat). After 16 weeks of the diet, FuFA (25mg/kg/day) was administered by gavage for the last 7 weeks. A glucose tolerance test was performed at week 4th. Tissues and blood were collected at week 7th after 5h fasting. Mass spectrometry, ELISA, and multiplex analysis were performed on plasma. Liver staining (H&E) was also performed to quantify steatosis and ballooning. Results The glucose tolerance test showed improved glucose clearance in FuFA-treated mice compared to vehicle. The fasting level of insulin and c-peptide 2 were respectively 2.9- and 1.5-fold lower in FuFA- compared to the vehicle-treated mice. Additionally, circulating TNF-α was significantly lower (1.6-fold) in FuFA-treated mice. NAFLD activity scores - hepatocytes ballooning and steatosis - were also significantly decreased in FuFA-treated mice by 1.6- and 1.4-fold, respectively. Finally, an MS-based analysis of plasma showed a significant decrease in cholesterol (1.2-fold) and cholesterol-ester (1.4-fold) levels in FuFA-treated mice. Conclusions In conclusion, the beneficial effects observed in Ω-3 and FO treatment on DIO and NAFLD may be related to the presence of FuFA in these dietary preparations. Funding Sources NIH.


2008 ◽  
Vol 159 (suppl_1) ◽  
pp. S67-S74 ◽  
Author(s):  
Francesco Chiarelli ◽  
Maria Loredana Marcovecchio

Childhood obesity is a significant health problem that has reached epidemic proportions around the world and is associated with several metabolic and cardiovascular complications. Insulin resistance is a common feature of childhood obesity and is considered to be an important link between adiposity and the associated risk of type 2 diabetes and cardiovascular disease. Insulin resistance is also a key component of the metabolic syndrome, and its prevalence in the paediatric population is increasing, particularly among obese children and adolescents. Several factors are implicated in the pathogenesis of obesity-related insulin resistance, such as increased free fatty acids and many hormones and cytokines released by adipose tissue.Valid and reliable methods are essential to assess the presence and the extent of insulin resistance, the associated risk factors and the effect of pharmacological and lifestyle interventions. The two most common tests to assess insulin resistance are the hyperinsulinemic euglycemic clamp and the frequently sampled i.v. glucose tolerance test utilizing the minimal model. However, both these tests are not easily accomplished, are time consuming, expensive and invasive. Simpler methods to assess insulin resistance based on surrogate markers derived from an oral glucose tolerance test or from fasting insulin and glucose levels have been validated in children and adolescents and widely used.Given the strong association between obesity, insulin resistance and the development of metabolic syndrome and cardiovascular disease, prevention and treatment of childhood obesity appear to be essential to prevent the development of insulin resistance and the associated complications.


Endocrinology ◽  
2009 ◽  
Vol 150 (11) ◽  
pp. 5192-5192
Author(s):  
Ayman M. Arafat ◽  
Martin O. Weickert ◽  
Jan Frystyk ◽  
Joachim Spranger ◽  
Christof Schöfl ◽  
...  

ABSTRACT Context: Insulin interacts with the GH-IGF system by a reciprocal regulation of IGF-binding proteins (IGFBP) and GH, which in turn regulate insulin sensitivity via bioactive IGF-I. This network is linked to metabolic syndrome and cardiovascular diseases. Objective: We evaluated the effect of glucose and insulin on IGFBP-1-4, particularly IGFBP-2, in the regulation of bioactive IGF-I and its relation to insulin resistance. Setting: The study was conducted at an endocrinology center. Research Design and Methods: Twenty-four healthy subjects (12 men; aged 21–72 yr; body mass index 25.9 ± 0.9 kg/m2) and 19 subjects with impaired glucose tolerance (IGT; eight men; aged 26–71 yr; body mass index 28.9 ± 1.2 kg/m2 ) were prospectively studied using oral glucose tolerance test and hyperinsulinemic euglycemic clamp. Results: During the clamp, insulin decreased IGF-I bioactivity in both IGT subjects and controls (−16.2 ± 2.8 and −13.9 ± 3.3%, respectively; P < 0.01). In addition, insulin increased IGFBP-2 and GH and decreased IGFBP-1 and -4 but did not alter total IGF-I, IGF-II, or IGFBP-3 levels. During the oral glucose tolerance test, GH and IGFBP-1 were markedly suppressed. Subjects with IGT showed more pronounced insulin resistance and lower GH, IGFBP-1, and IGFBP-2 levels (P < 0.05). In multiple regression analysis, IGFBP-2 was an independent predictor of insulin sensitivity (β = 0.36, P < 0.05) and IGF-I bioactivity (β = −0.5, P < 0.05). Conclusions: Our data indicate that insulin acutely decreases IGF-I bioactivity through differential modulation of IGFBPs. Furthermore, IGFBP-2 plays a central role in the insulin-IGF system cross talk and is closely linked to insulin resistance, thereby providing a further explanation for its association with the metabolic syndrome.


Diabetes ◽  
1967 ◽  
Vol 16 (3) ◽  
pp. 175-180 ◽  
Author(s):  
H. Nakamura ◽  
G. Faludi ◽  
J. J. Spitzer

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