Obesity and insulin resistance (IR) are interdependent multifactorial processes that cannot be understood separately. Obesity leads to systemic inflammation and increased levels of free fatty acids that provoke IR and lipotoxicity. At the same time, IR exacerbates adipose cell dysfunction, resulting in chronic inflammation and major lipotoxic effects on nonadipose tissues. 4-Hydroxyisoleucine (4-OHIle), a peculiar nonprotein amino acid isolated from fenugreek (Trigonella foenum-graecum) seeds, exhibits interesting effects on IR related to obesity. 4-OHIle increases glucose-induced insulin release, and the insulin response mediated by 4-OHIle depends on glucose concentration. The beneficial effects observed are related to the regulation of blood glucose, plasma triglycerides, total cholesterol, free fatty acid levels, and the improvement of liver function. The mechanism of action is related to increased Akt phosphorylation and reduced activation of Jun N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB. Here, we present a review of the research regarding the insulinotropic and insulin-sensitising activity of 4-OHIle in in vitro and in vivo models.
Objective: Protamine has been shown to have an inhibitory effect on protein lipase in vitro; the objective of this study was to evaluate the antiobesity activity effect of protamine in obese induced rats, and to evaluate the effect of protamine on postprandial hypertriacylglyceridemia in rats by intragastric administration of a lipid emulsion containing corn oil. Design: Two experiments were carried out: (1) In a parallel study in rats, we administered a lipid emulsion containing corn oil plus 0, 200 or 500 mg kg -1 of protamine intragastrically. (2) In a randomized parallel prospective rats experiment, rats were fed with a high-fat diet and 0, 200 or 500 mg of protamine per kg of animal weight during 5 weeks. Subjects: Male Sprague-Dawley rats. Measurements: In experiment 1, plasma triacylglycerol levels after oral administration of lipid emulsion were determined. In experiment 2, weight gain, concentrations of plasma triacylglycerol, plasma total cholesterol and albumin were determined, and the subcutaneous and visceral adipose tissues were weighed. Results: Plasma triacylglycerol concentration in rats administered with 200 or 500 mg kg -1 of protamine was significantly lower than that in rats in the control group (200 mg kg -1 of protamine, Po0.05 at 1, 2, 3 and 4 h; 500 mg kg -1 of protamine Po0.05 at 2, 3 and 4 h). In rats fed with a high-fat diet, and 200 and 500 mg kg -1 of protamine, there was a decreased body weight gain by 52 and 66 g, respectively, reduced visceral fat by 5 and 8 g, respectively and subcutaneous tissue weights by 12 and 15 g, respectively. Plasma triacylglycerol was 17 and 45 mg per 100 ml lower in rats fed with high-fat diet plus 200 and 500 mg kg -1 of protamine, respectively. And cholesterol concentrations were 18 and 22 mg per 100 ml lower in both protamine groups, respectively. Conclusion: Our study demonstrates that protamine reduce weight gain and body fat accumulation through the inhibition of dietary fat absorption.
In this study, we evaluated the effect of an analogue of L-carnitine on parameters involved with Metabolic Syndrome in obese Zucker rats. Twenty-four rats were treated for 5 weeks with L-carnitine (300 mg/kg) and its analogue at two concentrations (100 and 250 mg/kg) to assess their impact on glucose, triglycerides and cholesterol in liver and blood samples, as well as the amount of liver glycogen. Liver slices were also analysed. The analogue reduced the levels of glucose, triglycerides and cholesterol in liver and the level of triglycerides in serum. At 100 mg/kg, the analogue proved more effective than L-carnitine in improving the biochemical alterations present in liver. The amount of liver glycogen content was higher in obese animals treated with both L-carnitine and the analogue. No changes on insulin and leptin were observed in animals treated. L-carnitine and its analogue reduced the microvesicular fatty infiltration in liver. This study demonstrated that the analogue tested is more potent and efficient than L-carnitine and improves the pharmacological profile of L-carnitine.Metabolic syndrome, syndrome 'X' or insulin resistance syndrome has been the focus of attention during the past 80 years [1]. Its importance lies in its multiple, interrelated risk factors for metabolic origin, which can lead to the development of diseases such as atherosclerosis, type 2 diabetes mellitus, dyslipidaemia, high blood pressure, elevated plasma glucose, prothrombotic state and pro-inflammatory state [2]. Other factors associated with metabolic syndrome are abdominal obesity, insulin resistance and cardiovascular diseases (CVD) [3]. The main causes for the increase in the disease are obesity and diabetes mellitus among populations with a sedentary life pattern [4,5].L-carnitine is synthesized by mammals as a result of the synthesis of amino acids such as lysine or methionine and is also obtained from the diet [6,7]. Carnitine is an essential factor in transporting the long-chain fatty acids (acyl CoA) from the cytoplasm into the mitochondria where the beta-oxidation takes place [8]. A large body of evidence suggests that carnitine and its derivatives acetyl-L-carnitine and propionyl-L-carnitine enhance glucose utilization by stimulating the activity of pyruvate dehydrogenase complex [9], which is a key enzymatic complex in glucose oxidation, because intramitochondrial acetyl-CoA can be converted with carnitine into acetyl-L-carnitine (ALC) via the carnitine acetyltransferase that is then transported out of the mitochondria [10]. L-Carnitine is an amine key substrate in a family of carnitine acyltransferases, transferred reversibly between active units of acyl carnitine and co-enzyme A to preserve homoeostasis for a wide range of traffic that are crucial for acyl intermediary metabolism and cellular regulation [11].Various analogues of L-carnitine have been synthesized to study their mode of action and the structural features of their binding sites [12,13]. The phosphorus analogues of naturally occurring amino ac...
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