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Acetyl carnitine AND insulin resistance

María M Adeva-Andany, Laura López-Maside, Cristóbal Donapetry-García, Carlos Fernández-Fernández, Cristina Sixto-Leal
Branched-chain amino acids (leucine, isoleucine and valine) are structurally related to branched-chain fatty acids. Leucine is 2-amino-4-methyl-pentanoic acid, isoleucine is 2-amino-3-methyl-pentanoic acid, and valine is 2-amino-3-methyl-butanoic acid. Similar to fatty acid oxidation, leucine and isoleucine produce acetyl-coA. Additionally, leucine generates acetoacetate and isoleucine yields propionyl-coA. Valine oxidation produces propionyl-coA, which is converted into methylmalonyl-coA and succinyl-coA. Branched-chain aminotransferase catalyzes the first reaction in the catabolic pathway of branched-chain amino acids, a reversible transamination that converts branched-chain amino acids into branched-chain ketoacids...
June 2017: Amino Acids
Yasunori Miyamoto, Teruo Miyazaki, Akira Honda, Homare Shimohata, Kouichi Hirayama, Masaki Kobayashi
Insulin resistance occurs frequently in patients with chronic kidney disease. However, the mechanisms of insulin resistance associated with chronic kidney disease are unclear. It is known that an increase in the mitochondrial acetyl-CoA (AcCoA)/CoA ratio causes insulin resistance in skeletal muscle, and this ratio is regulated by carnitine acetyltransferase that exchanges acetyl moiety between CoA and carnitine. Because excess acetyl moiety of AcCoA is excreted in urine as acetylcarnitine, we hypothesized that retention of acetylcarnitine might be a cause of insulin resistance in chronic kidney disease patients...
November 2016: Journal of Clinical Biochemistry and Nutrition
Shengnan Wei, Ming Zhang, Yang Yu, Huan Xue, Xiaoxin Lan, Shuping Liu, Grant Hatch, Li Chen
Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells...
November 15, 2016: European Journal of Pharmacology
Benedetta Bigio, Aleksander A Mathé, Vasco C Sousa, Danielle Zelli, Per Svenningsson, Bruce S McEwen, Carla Nasca
Although regulation of energy metabolism has been linked with multiple disorders, its role in depression and responsiveness to antidepressants is less known. We found that an epigenetic and energetic agent, acetyl-l-carnitine (LAC, oral administration), rapidly rescued the depressive- and central and systemic metabolic-like phenotype of LAC-deficient Flinders Sensitive Line rats (FSL). After acute stress during LAC treatment, a subset of FSL continued to respond to LAC (rFSL), whereas the other subset did not (nrFSL)...
July 12, 2016: Proceedings of the National Academy of Sciences of the United States of America
Shigeo Shinohara, Yuanjun Gu, Ying Yang, Yasuo Furuta, Masahiko Tanaka, Xiaohua Yue, Weiqing Wang, Masaru Kitano, Hiroshi Kimura
Desi-type chickpeas, which have long been used as a natural treatment for diabetes, have been reported to lower visceral adiposity, dyslipidemia and insulin resistance induced by a chronic high-fat diet in rats. In this study, in order to examine the effects of chickpeas of this type in an in vitro system, we used the 3T3-L1 mouse cell line, a subclone of Swiss 3T3 cells, which can differentiate into cells with an adipocyte-like phenotype, and we used ethanol extracts of chickpeas (ECP) instead of chickpeas...
August 2016: International Journal of Molecular Medicine
Jarinyaporn Naowaboot, Supaporn Wannasiri, Patchareewan Pannangpetch
Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured...
June 2016: Journal of Physiology and Biochemistry
Mi Young Song, Seok Yong Kang, Tae Woo Oh, Rethineswaran Vinoth Kumar, Hyo Won Jung, Yong-Ki Park
The root of Atractylodes macrocephala Koidzumi (Atractylodis Rhizoma Alba, ARA) is a Traditional Korean Medicine and has been commonly used for weight control. Mitochondrial dysfunction appears to be a key contributor to insulin resistance, and therefore mitochondrial targeting drugs represent an important potential strategy for the treatment of insulin resistance and obesity. In this study, the authors investigated the regulatory effects of ARA on mitochondrial function with respect to the stimulation of glucose and lipid metabolism in C2C12 myotubes...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
Chen-Xu Ge, Rong Yu, Min-Xuan Xu, Pei-Qin Li, Chen-Yu Fan, Jian-Mei Li, Ling-Dong Kong
Betaine has been proven effective in treating nonalcoholic fatty liver disease (NAFLD) in animal models, however, its molecular mechanisms remain elusive. The aims of this study were to explore the mechanisms mediating the anti-inflammatory and anti-lipogenic actions of betaine in fructose-fed rats. In this study, betaine improved insulin resistance, reduced body weight gain and serum lipid levels, and prevented hepatic lipid accumulation in fructose-fed rats. It up-regulated hepatic expression of liver X receptor-alpha (LXRα) and peroxisome proliferator-activated receptor-alpha (PPARα), with the attenuation of the changes of their target genes, including hepatic carnitine palmitoyl transferase (CPT) 1α, glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1, apolipoprotein B, sterol regulatory element-binding protein 1c and adipocyte differentiation-related protein, involved in fatty acid oxidation and lipid storage in these model rats...
January 5, 2016: European Journal of Pharmacology
Jarinyaporn Naowaboot, Pritsana Piyabhan, Narongsuk Munkong, Wason Parklak, Patchareewan Pannangpetch
Ferulic acid (FA) is a plant phenolic acid that has several pharmacological effects including antihyperglycaemic activity. Thus, the objective of this study is to investigate the effect of FA on glucose and lipid metabolism in high-fat diet (HFD)-induced obese mice. Institute for Cancer Research (ICR) mice were fed a HFD (45 kcal% fat) for 16 weeks. At the ninth week of induction, the obese mice were orally administered with daily FA doses of 25 and 50 mg/kg for the next eight weeks. The results show that FA significantly reduced the elevated blood glucose and serum leptin levels, lowered the insulin resistance, and increased the serum adiponectin level...
February 2016: Clinical and Experimental Pharmacology & Physiology
Parim Brahma Naidu, V V Sathibabu Uddandrao, Ramavat Ravindar Naik, Pothani Suresh, Balaji Meriga, Mustapha Shabana Begum, Rajesh Pandiyan, Ganapathy Saravanan
Obesity, generally linked to hyperlipidemia, has been occurring of late with distressing alarm and has now become a global phenomenon casting a huge economic burden on the health care system of countries around the world. The present study investigated the effects of gingerol over 30 days on the changes in HFD-induced obese rats in marker enzymes of lipid metabolism such as fatty-acid synthase (FAS), Acetyl CoA Carboxylase (ACC), Carnitine Palmitoyl Transferase-1(CPT-1), HMG co-A Reductase (HMGR), Lecithin Choline Acyl Transferase (LCAT) and Lipoprotein Lipase (LPL) and inflammatory markers (TNF-α and IL-6)...
January 5, 2016: Molecular and Cellular Endocrinology
Daniel F Vatner, Jaclyn Snikeris, Violeta Popov, Rachel J Perry, Yasmeen Rahimi, Varman T Samuel
Thyroid hormone mimetics are alluring potential therapies for diseases like dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and insulin resistance. Though diiodothyronines are thought inactive, pharmacologic treatment with 3,5- Diiodo-L-Thyronine (T2) reportedly reduces hepatic lipid content and improves glucose tolerance in fat-fed male rats. To test this, male Sprague Dawley rats fed a safflower-oil based high-fat diet were treated with T2 (0.25 mg/kg-d) or vehicle. Neither 10 nor 30 days of T2 treatment had an effect on weight, adiposity, plasma fatty acids, or hepatic steatosis...
2015: PloS One
Kyung-A Hwang, Yu-Jin Hwang, Ga Ram Kim, Jeong-Sook Choe
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common liver disease that is strongly associated with obesity and dysregulation of insulin in the liver. However, currently no pharmacological agents have been established for the treatment of NAFLD. In this regard, we sought to evaluate the anti-NAFLD effects of Aralia elata (Miq) Seem (AE) extract and its ability to inhibit hepatic lipid accumulation and modulate cellular signaling in a high fat diet (HFD)-induced obese mouse model...
2015: BMC Complementary and Alternative Medicine
Andreas Mæchel Fritzen, Anne-Marie Lundsgaard, Andreas Børsting Jordy, Sanne Kellebjerg Poulsen, Steen Stender, Henriette Pilegaard, Arne Astrup, Thomas Meinert Larsen, Jørgen F P Wojtaszewski, Erik A Richter, Bente Kiens
CONTEXT: The molecular mechanisms behind diet-induced metabolic improvements remain to be studied. OBJECTIVE: This study sought to investigate whether expression of proteins in skeletal muscle or adipose tissue could explain improvements in glucose and lipid homeostasis after weight loss. DESIGN: Volunteers consumed a New Nordic Diet (NND) or an Average Danish Diet for 26 weeks in a controlled, free-living setting. SUBJECTS: Sixty four moderately obese women and men (44 ± 2 y; body mass index, 31 ± 1 kg/m(2))...
September 2015: Journal of Clinical Endocrinology and Metabolism
Marilyne Labrie, Simon Lalonde, Ouafa Najyb, Maxime Thiery, Caroline Daneault, Chrisitne Des Rosiers, Eric Rassart, Catherine Mounier
Transgenic mice (Tg) overexpressing human apolipoprotein D (H-apoD) in the brain are resistant to neurodegeneration. Despite the use of a neuron-specific promoter to generate the Tg mice, they expressed significant levels of H-apoD in both plasma and liver and they slowly develop hepatic steatosis and insulin resistance. We show here that hepatic PPARγ expression in Tg mice is increased by 2-fold compared to wild type (WT) mice. Consequently, PPARγ target genes Plin2 and Cide A/C are overexpressed, leading to increased lipid droplets formation...
2015: PloS One
Daniela Macconi, Luca Perico, Lorena Longaretti, Marina Morigi, Paola Cassis, Simona Buelli, Norberto Perico, Giuseppe Remuzzi, Ariela Benigni
BACKGROUND: Angiotensin II promotes insulin resistance. The mechanism underlying this abnormality, however, is still poorly defined. In a different setting, skeletal muscle metabolism and insulin signaling are regulated by Sirtuin3. OBJECTIVE: Here, we investigate whether angiotensin II-induced insulin resistance in skeletal muscle is associated with Sirtuin3 dysregulation and whether pharmacological manipulation of Sirtuin3 confers protection. STUDY DESIGN: Parental and GLUT4-myc L6 rat skeletal muscle cells exposed to angiotensin II are used as in vitro models of insulin resistance...
2015: PloS One
Su Gao, Ryan P McMillan, Qingzhang Zhu, Gary D Lopaschuk, Matthew W Hulver, Andrew A Butler
OBJECTIVE: The peptide hormone adropin regulates fuel selection preferences in skeletal muscle under fed and fasted conditions. Here, we investigated whether adropin treatment can ameliorate the dysregulation of fuel substrate metabolism, and improve aspects of glucose homeostasis in diet-induced obesity (DIO) with insulin resistance. METHODS: DIO C57BL/6 mice maintained on a 60% kcal fat diet received five intraperitoneal (i.p.) injections of the bioactive peptide adropin(34-76) (450 nmol/kg/i...
April 2015: Molecular Metabolism
Yuwen Li, Tiejun Zhang, Jia Cui, Na Jia, Yin Wu, Miaomiao Xi, Aidong Wen
OBJECTIVES: The aim of this study is to investigate antidiabetic effects and molecular mechanisms of the chemical Chikusetsu saponin IVa (CHS) that isolated from root bark of Aralia taibaiensis, which has multiple pharmacological activity, such as relieving rheumatism, promoting blood circulation to arrest pain and antidiabetic action. METHODS: Rats with streptozotocin/nicotinamide-induced type 2 diabetes mellitus (T2DM) and insulin-resistant myocytes were used...
July 2015: Journal of Pharmacy and Pharmacology
Yasmeen Rahimi, João-Paulo G Camporez, Max C Petersen, Dominik Pesta, Rachel J Perry, Michael J Jurczak, Gary W Cline, Gerald I Shulman
The pyruvate dehydrogenase complex (PDH) has been hypothesized to link lipid exposure to skeletal muscle insulin resistance through a glucose-fatty acid cycle in which increased fatty acid oxidation increases acetyl-CoA concentrations, thereby inactivating PDH and decreasing glucose oxidation. However, whether fatty acids induce insulin resistance by decreasing PDH flux remains unknown. To genetically examine this hypothesis we assessed relative rates of pyruvate dehydrogenase flux/mitochondrial oxidative flux and insulin-stimulated rates of muscle glucose metabolism in awake mice lacking pyruvate dehydrogenase kinase 2 and 4 [double knockout (DKO)], which results in constitutively activated PDH...
November 18, 2014: Proceedings of the National Academy of Sciences of the United States of America
Zhiguo Zhang, Shudong Wang, Shanshan Zhou, Xiaoqing Yan, Yonggang Wang, Jing Chen, Nicholas Mellen, Maiying Kong, Junlian Gu, Yi Tan, Yang Zheng, Lu Cai
Type 2 diabetes mellitus (T2DM)-induced cardiomyopathy is associated with cardiac oxidative stress, inflammation, and remodeling. Sulforaphane (SFN), an isothiocyanate naturally presenting in widely consumed vegetables, particularly broccoli, plays an important role in cardiac protection from diabetes. We investigated the effect of SFN on T2DM-induced cardiac lipid accumulation and subsequent cardiomyopathy. Male C57BL/6J mice were fed a high-fat diet for 3months to induce insulin resistance, followed by a treatment with 100mg/kg body-weight streptozotocin to induce hyperglycemia; we referred to it as the T2DM mouse model...
December 2014: Journal of Molecular and Cellular Cardiology
Chenlin Ji, Yanyan Dai, Weiwei Jiang, Juan Liu, Miao Hou, Junle Wang, Jonas Burén, Xiaonan Li
Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet...
November 2014: Journal of Nutritional Biochemistry
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