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James R Levy

Publications and source records attributed to James R Levy.

7 recordsLinked to original sources

Differential effect of saturated and polyunsaturated fatty acids on hepatic glucose metabolism in humans.

Prolonged infusions of lipid and heparin that achieve high physiological free fatty acid (FFA) concentrations inhibit hepatic (and peripheral) insulin sensitivity in humans. These infusions are composed largely of polyunsaturated fatty acids (PUFA; linoleic and linolenic). It is not known whether fatty acid composition per se affects hepatic glucose metabolism in humans. To address this issue, we examined the impact of enteral infusions of either palm oil (48% palmitic, 35% oleic, and 8% linoleic acids) or safflower oil (6% palmitic, 12% oleic, 74% linoleic acids) in 14 obese nondiabetic subjects. (2)H(2)O was administered to determine the contribution of gluconeogenesis to endogenous glucose production (EGP), and a primed continuous infusion of [6,6-(2)H]glucose was administered to assess glucose appearance. As a result of the lipid infusions, plasma FFA concentrations increased significantly in both the palm oil (507.5 +/- 47.4 to 939.3 +/- 61.3 micromol/l, P < 0.01) and safflower oil (588.2.0 +/- 43.0 to 857.8 +/- 68.7 micromol/l, P < 0.01) groups after 4 h. EGP was similar at baseline (12.4 +/- 1.8 vs. 11.2 +/- 1.0 micromol x kg FFM(-1) x min(-1)). During a somatostatin-insulin clamp, the glucose infusion rate was significantly lower (AUC glucose infusion rate 195.8 +/- 50.7 vs. 377.8 +/- 38.0 micromol/kg FFM, P < 0.01), and rates of EGP were significantly higher (10.7 +/- 1.4 vs. 6.5 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < 0.01) after palm oil compared with safflower oil, respectively. Baseline rates of gluconeogenesis and glycogenolysis were also similar. However, after lipid infusion, rates of glycogenolysis were suppressed by safflower oil but not by palm oil. Thus these studies demonstrate, for the first time in humans, a differential effect of saturated fatty acids and PUFA on hepatic glucose metabolism.

Adult↗

Plasma hyperosmolality stimulates leptin secretion acutely by a vasopressin-adrenal mechanism.

Glucose administration to rodents acutely stimulates leptin secretion. To investigate the mechanism, rats were infused intravenously with various concentrations of glucose, and plasma leptin concentrations were measured with time. The osmolality of the infusates was equalized with various concentrations of carbohydrates that are not metabolized. Hyperosmolar glucose stimulates leptin secretion in a dose-dependent manner, with peak plasma leptin concentrations occurring approximately 3 h after the end of the glucose infusion. Hypertonic infusions of galactose, mannitol, and sodium chloride independently stimulate leptin secretion with approximately one-half the strength of equivalent osmolar concentrations of glucose. Peak plasma leptin concentrations occur approximately 4 h after the end of the hypertonic solution infusion. Hypertonic solutions of mannitol do not stimulate leptin secretion in vasopressin-deficient or in adrenalectomized animals. In conclusion, intravenous infusions of hypertonic glucose and hypertonic mannitol independently stimulate leptin secretion. Hyperosmolality stimulates leptin secretion by a vasopressin-adrenal mechanism.

Adipose Tissue↗

Dietary n-3 polyunsaturated fatty acids decrease hepatic triglycerides in Fischer 344 rats.

Dietary fatty acid composition modifies hepatic lipid metabolism. To determine the effects of fatty acids on hepatic triglyceride storage, rats were fed diets enriched in carbohydrates (control), fish oil, or lard. After 4 weeks, the animals were fasted overnight. In the morning, the animals were either sacrificed or fed 8 g of their respective diets before sacrifice. Animals ingested more food calories with diets containing fish oil than with other diets. However, fish oil-fed animals weighed less and had less body fat. In fish oil-fed animals, liver triglyceride was lower by 27% (P <.05) and 73% (P <.01) than in control- and lard-fed animals, respectively. Fish oil altered the postprandial gene expression of hepatic regulators of fatty acid degradation and synthesis. Fish oil feeding blunted the normal postprandial decline in fatty acid degradation genes (PPARalpha, CPT1, and ACO) and blunted the normal postprandial rise in triglyceride synthesis genes (SREBP1-c, FAS, SCD-1). Therefore, the direct postprandial effect of fish oil ingestion decreases the propensity for hepatic triglyceride storage. In conclusion, n-3 polyunsaturated fatty acids decrease total body weight, total body fat, and hepatic steatosis.

Animals↗

An unusual cause of autonomic dysreflexia: pheochromocytoma in an individual with tetraplegia.

BACKGROUND: Autonomic dysreflexia (AD) is a frequent, serious acute syndrome that occurs in patients with spinal cord lesions at level T6 and above. The syndrome is caused by massive sympathetic discharge that is triggered by a noxious stimulus below the level of the spinal cord lesion. Pheochromocytomas are rare tumors that present with symptoms similar to AD. METHODS: Case Report. FINDINGS: A 50-year-old man with C7 American Spinal Injury Association scale A tetraplegia presented with episodes of severe headaches and paroxysmal hypertension. He was diagnosed with AD. Despite resolving bladder and bowel problems, he continued to have hypertensive episodes. A CT scan of the abdomen revealed a heterogeneous left adrenal mass. Further workup revealed significantly elevated serum and 24-hour urinary catecholamines. Clonidine failed to fully suppress the markedly elevated concentrations of serum catecholamines. These biochemical findings were consistent with the diagnosis of pheochromocytoma. Prior to surgery, the patient was treated with alpha-receptor blockers and volume expansion with intravenous fluids. A left adrenalectomy was performed. The surgical specimen revealed that the adrenal gland was expanded by a spherical mass. The pathologic report was benign pheochromocytoma of the left adrenal gland. CONCLUSION: Clinical symptoms and hypertensive episodes resolved following adrenalectomy. To our knowledge, this is the first reported case of a pheochromocytoma in an individual with spinal cord injury.

Adrenal Gland Neoplasms↗

Lipid metabolism and resistin gene expression in insulin-resistant Fischer 344 rats.

The interrelationship between insulin and leptin resistance in young Fischer 344 (F344) rats was studied. Young F344 and Sprague-Dawley (SD) rats were fed regular chow. F344 animals had two- to threefold higher insulin and triglyceride concentrations and increased stores of triglycerides within liver and muscle. F344 animals gained more body fat. Both acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase I gene expression were 20-50% less in F344 animals than in age-matched SD animals. Peroxisome proliferator-activated receptor-alpha gene expression was reduced in 70-day-old F344 animals. Finally, resistin gene expression was similar in 70-day-old SD and F344 animals. Resistin gene expression increased fivefold in F344 animals and twofold in SD animals from 70 to 130 days, without a change in insulin sensitivity. We conclude that young F344 animals have both insulin and leptin resistance, which may lead to diminished fatty oxidation and accumulation of triglycerides in insulin-sensitive target tissues. We did not detect a role for resistin in the etiology of insulin resistance in F344 animals.

Acyl-CoA Oxidase↗

Safety of an immune-enhancing nutrition supplement in cirrhotic patients with history of encephalopathy.

Malnutrition in advanced cirrhosis may worsen liver function and increase susceptibility to infections. Immune-enhancing nutrition supplements (IENS) may be of value, but their safety in patients with decompensated cirrhosis and history of encephalopathy is unknown. We assessed the safety of Impact Recover (Novartis, St. Louis Park, MN), an orally palatable IENS, in 12 men with hepatic cirrhosis of Child-Turcotte-Pugh (CTP) class B or C, ages 40-60. On day 0, patients were evaluated serially for 6 hours after ingestion of 2 packets of Impact Recover. Despite a transient doubling of the blood ammonia, no cognitive abnormalities were noted on clinical assessment or psychometric testing. Subsequently, patients were instructed to ingest 3 packets per day of Impact Recover for 56 days, after which supplements were stopped. Patients were evaluated in a fasting state on days 0 (baseline), 56 (end of treatment), and 112 (follow-up). One patient was transplanted on day 21, and another died after an urgent cholecystectomy on day 30. The remaining 10 patients completed the study. Mean value of CTP score was 9 (range, 7-11) and mean value of model for end-stage liver disease (MELD) score was 14 (7-21), and there was no change after 8 weeks of IENS. Only 1 experienced transient worsening of encephalopathy after omitting lactulose. Performances on psychometric tests did not change. Transferrin levels increased rapidly with IENS, then returned toward baseline after IENS was stopped. Fasting insulin and peptide YY (PYY) levels also increased, but fasting glucose and hemoglobin A1C did not change. Trends in other nutrition and immune parameters did not reach significance. We conclude that acute and chronic administration of Impact Recover was well tolerated in cirrhotic patients with controlled encephalopathy. Further studies are justified to assess potential efficacy of long-term IENS in preventing infection and slowing progression in advanced cirrhosis.

Adult↗