Effects of benfluorex on in vivo patterns of insulin resistance induced by diets rich in fat or fructose

Storlien, Leonard H; Pan, Di; Kusunoki, Masataka; Cooney, Gregory J.

doi:10.1002/dmr.5610090511

Cited by 9 publications

(4 citation statements)

References 35 publications

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“…1). This is reminiscent of the well known insulin resistance state of tnuscle from animals fed a diet rich in fat [34]. Our results suggest that the PEPCK gene may also be a target of insulin resistance in adipose tissue.…”

Section: Inscussionmentioning

confidence: 70%

Fatty Acids and Fibrates are Potent Inducers of Transcription of the Phosphenol pyruvate Carboxykinase Gene in Adipocytes

Antras-Ferry

Robin

et al. 1995

European Journal of Biochemistry

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Cytosolic phosphoPnolpyruvate carboxykinase (PEPCK) plays a critical role in adipose tissue glyccroneogenesis. We havc previously shown that transcription of the PEPCK gene was stimulated by isoprend i n e and relinoic acid in 3T3-E'442A adipocytes. We. also showed that oleate increased PEPCK mRNA. Here, we analysed the effect that fatty acids of various chain lengths and unsaturation degrces exerted on PEPCK gene expression in 3T3-F442A adipocytes. Whcn maintained in scrum-free, glucose-free medium, differentiated cells responded to unsaturated long-chain fatty acids by a large increase in PEPCK mRNA whereas saturated fatty acids were inefficient. A maximum fivefold stimulation by oleate was attained at 4 h of treatment with 1 mM fatty acid bound to albumin i n a 6: 1 ratio. The poly-unsaturated very longchain fatty acid all-cis-4,7,10,'13,16,19-docosahcxaenoic acid (C,,,,) was even more potent and produced a tenfold increase. The expression of the genes encoding glycerol-3-phosphate dehydrogenase, hormonesensitive lipase or actin remained unaffected by oleate exposure. A 4-h treatment by the hypolipidemic drug clofibrate, 0.5-2 mM, also produccd a large (3-9-fold) increase in PEPCK mRNA. When used at non-saturating concentrations, oleate and clofibrate acted in an additive manner. At maximally effective concentrations, additivity was lost, suggesting that fatty acids and fibrates might act through similar mechanisms. Nuclear transcription experiments showed that olcate and clofibrate stimulated the transcription rate of the gene. 3T3-F442A cells were stably transfected with it plasmid containing the base pairs -2100 to +69 of the PEPCK gene promoter fused to the chloramphenicol acetyltransferase gene. These differentiated stable transfectants responded to oleate and clofibrrite by a specific increase in chloramphenicol acetyltransferasc activity. Adipocytes express various isoforms of peroxisomc-proliferator-activated receptors that can be activated by fibrates and fatty acids. Potcntial recognition sequences for peroxisomeproliferator-activated receptors are present in the -2100 to +69 fragment of thc PEPCK gene promoter. Thus, this gene represents an ideal molecular target for undersianding the complex transcriptional control excrted by fatty acids and peroxisomc proliferators.

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Section: Inscussionmentioning

confidence: 70%

Fatty Acids and Fibrates are Potent Inducers of Transcription of the Phosphenol pyruvate Carboxykinase Gene in Adipocytes

Antras-Ferry

Robin

et al. 1995

European Journal of Biochemistry

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“…Previous studies have demonstrated that fatty acids are taken up across the vesicle membrane, with small cytoplasmic fatty acid-binding proteins likely acting as a luminal sink (49). Fatty acid transport into membrane vesicles was carried out as previously described (39,40,49).…”

Section: Artificial Rearing Of Rat Pupsmentioning

confidence: 99%

“…We hypothesized that exposure to a diet containing fructose during the suckling period would program metabolism in such a way to promote increased body weight in adulthood. Because high‐fructose diets fed to rodents are known to cause insulin resistance in skeletal muscle (39), adipose tissue (40), and liver (41), we examined fatty acid transport in these three tissues as possible target tissues of metabolic programming effects.…”

Section: Introductionmentioning

confidence: 99%

Dietary Fructose During the Suckling Period Increases Body Weight and Fatty Acid Uptake Into Skeletal Muscle in Adult Rats

Huynh

Luiken

Coumans

et al. 2008

Obesity

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objective:The suckling period is one potentially "critical" period during which nutritional intake may permanently "program" metabolism to promote increased adult body weight and insulin resistance in later life. This study determined whether fructose introduced during the suckling period altered body weight and induced changes in fatty acid transport leading to insulin resistance in adulthood in rats. Methods and Procedures: Pups were randomly assigned to one of four diets: suckle controls (SCs), rat milk substitute formula (Rat Milk Substitute), fructose-containing formula (Fructose), or galactose-containing formula (Galactose). Starting at weaning, all pups received the same diet; at 8 weeks of age, half of the SC rats began ingesting a diet containing 65% kcal fructose (SC-Fructose). This continued until animals were 12 weeks old and the study ended. Results: At weeks 8, 10, and 11, the Fructose group weighed more than SC and SC-Fructose groups (P < 0.05). At weeks 8 and 10 of age, the Fructose group had significantly higher insulin concentrations vs. rats in the SC-Fructose group. 3 H-Palmitate transport into vesicles from hind limb skeletal muscle was higher in Fructose vs. SC rats (P < 0.05). CD36 expression was increased in the sarcolemma but not in whole tissue homogenates from skeletal muscle from Fructose rats (P < 0.05) suggesting a redistribution of this protein associated with fatty acid uptake across the plasma membrane. This change in subcellular localization of CD36 is associated with insulin resistance in muscle. Discussion: Consuming fructose during suckling may result in lifelong changes in body weight, insulin secretion, and fatty acid transport involving CD36 in muscle and ultimately promote insulin resistance.

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“…Mounting evidence indicates that insulin resistance is highly associated with excessive intramyocellular triglyceride accumulation [ 36 – 38 ]. High fructose diets are known to cause insulin resistance [ 39 ] and triglyceride accumulation [ 40 ] in the skeletal muscle of rodents. In healthy subjects with and without a family history of type 2 diabetes, fructose overconsumption also increases lipid accumulation in skeletal muscle [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Treatment with Rhodiola crenulata root extract ameliorates insulin resistance in fructose-fed rats by modulating sarcolemmal and intracellular fatty acid translocase/CD36 redistribution in skeletal muscle

Chen

Yao

et al. 2016

BMC Complement Altern Med

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BackgroundRhodiola species have been used for asthenia, depression, fatigue, poor work performance and cardiovascular diseases, all of which may be associated with insulin resistance. To disclose the underlying mechanisms of action, the effect of Rhodiola crenulata root (RCR) on insulin resistance was investigated.MethodsMale Sprague-Dawley rats were treated with liquid fructose in their drinking water over 18 weeks. The extract of RCR was co-administered (once daily by oral gavage) during the last 5 weeks. The indexes of lipid and glucose homeostasis were determined enzymatically and/or by ELISA. Gene expression was analyzed by Real-time PCR, Western blot and/or confocal immunofluorescence.ResultsRCR extract (50 mg/kg) suppressed fructose-induced hyperinsulinemia and the increases in the homeostasis model assessment of insulin resistance index and the adipose tissue insulin resistance index in rats. Additionally, this treatment had a trend to restore the ratios of glucose to insulin and non-esterified fatty acids (NEFA) to insulin. Mechanistically, RCR suppressed fructose-induced acceleration of the clearance of plasma NEFA during oral glucose tolerance test (OGTT), and decreased triglyceride content and Oil Red O staining area in the gastrocnemius. Furthermore, RCR restored fructose-induced sarcolemmal overexpression and intracellular less distribution of fatty acid translocase/CD36 that contributes to etiology of insulin resistance by facilitating fatty acid uptake.ConclusionThese results suggest that RCR ameliorates insulin resistance in fructose-fed rats by modulating sarcolemmal and intracellular CD36 redistribution in the skeletal muscle. Our findings may provide a better understanding of the traditional use of Rhodila species.

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Effects of benfluorex on in vivo patterns of insulin resistance induced by diets rich in fat or fructose

Cited by 9 publications

References 35 publications

Fatty Acids and Fibrates are Potent Inducers of Transcription of the Phosphenol pyruvate Carboxykinase Gene in Adipocytes

Fatty Acids and Fibrates are Potent Inducers of Transcription of the Phosphenol pyruvate Carboxykinase Gene in Adipocytes

Dietary Fructose During the Suckling Period Increases Body Weight and Fatty Acid Uptake Into Skeletal Muscle in Adult Rats

Treatment with Rhodiola crenulata root extract ameliorates insulin resistance in fructose-fed rats by modulating sarcolemmal and intracellular fatty acid translocase/CD36 redistribution in skeletal muscle

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