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Biomedical subjects

R H Eckel

Publications and source records attributed to R H Eckel.

At least 19 recordsLinked to original sources
PubMed2004

Measurement of abdominal fat by CT compared to waist circumference and BMI in explaining the presence of coronary calcium.

OBJECTIVE: To evaluate the association between standard and computed tomography (CT)-based measures of obesity and subclinical atherosclerosis, defined as coronary artery calcium (CAC) by Electron Beam Computed Tomography (EBCT). DESIGN: Cross-sectional, observational study of anthropometric and CT obesity measures and presence of CAC. SUBJECTS: Participants were 383 men and 379 women, aged 20-58 y and asymptomatic for coronary artery disease (CAD). MEASUREMENTS: Intra-abdominal fat (IAF) and subcutaneous fat (SQF) were measured at the level of lumbar 2-3 and 4-5 spaces, using EBCT. Body mass index (BMI) was calculated from height and weight, and minimum waist circumference and maximum hip circumference were measured. CAC was measured by EBCT. RESULTS: In both men and women, BMI, waist circumference, IAF, and SQF were significantly related to CAC. However, BMI or waist circumference explained variation in the presence of CAC as well as IAF or SQF, univariately and after adjustment for additional cardiovascular risk factors. CONCLUSION: CT-based obesity exposure measures are not superior to BMI or waist circumference in association studies of subclinical CAD.

Abdominal Wall↗
PubMed2004

Lipid metabolism and nutrient partitioning strategies.

The increasing prevalence of overweight and obesity worldwide is daunting and requires prompt attention by the affected, health care profession, government and the pharmaceutical industry. Because overweight/obesity are defined as an excess of adipose tissue mass, all approaches in prevention and treatment must consider redirecting lipid storage in adipose tissue to oxidative metabolism. Lipid partitioning is a complex process that involves interaction between fat and other macronutrients, particularly carbohydrate. In an isocaloric environment, when fat is stored carbohydrate is oxidized and vice versa. Processes that influence fat partitioning in a manner in which weight is maintained must be modified by changes in organ-specific fat transport and metabolism. When therapy is considered, however, changes in lipid partitioning alone will be ineffective unless a negative energy balance is also achieved, i.e. energy expenditure exceeds energy intake. The intent of this review is to focus on molecules including hormones, enzymes, cytokines, membrane transport proteins, and transcription factors directly involved in fat trafficking and partitioning that could be potential drug targets. Some examples of favorably altering body composition by systemic and/or tissue specific modification of these molecules have already been provided with gene knockout and/or transgenic approaches in mice. The translation of this science to humans remains a challenging task.

Anti-Obesity Agents↗
PubMed2002

Sciatic nerve lipoprotein lipase is reduced in streptozotocin-induced diabetes and corrected by insulin.

The metabolic abnormalities underlying the cause of diabetic neuropathy have been the subject of much debate. Lipoprotein lipase (LPL) is a 56-kDa enzyme produced by several tissues in the body and has recently been shown in vitro to be expressed in cultured Schwann cells, where it is important in phospholipid synthesis. This suggests a role for LPL in myelin biosynthesis in the peripheral nervous system. The aim of this study was to determine if acute streptozotocin (STZ)-induced diabetes reduces the expression and regulation of sciatic nerve LPL in vivo. Adult Sprague Dawley rats were rendered diabetic via an sc injection of STZ. A decrease in sciatic nerve LPL activity was observed in the STZ-treated rats after just 2 d of diabetes and remained significantly reduced for at least 35 d. The decrease in LPL activity coincided temporally with a drop in motor nerve conduction velocity. Treatment with insulin for 4 d showed a normalization of sciatic nerve LPL activity. These results show that STZ-induced diabetes causes a decrease in LPL activity in the sciatic nerve that, as in other tissues, is reversible with insulin treatment. These data may suggest a role for LPL in the pathophysiology of diabetic neuropathy.

Animals↗
PubMed2001

Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome.

OBJECTIVE: To examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DESIGN: Cross-sectional study. SETTING: HIV primary care practices. PATIENTS: PI-treated patients with lipodystrophy (n= 14) and PI-treated (n= 13) and PI-naive (n= 5) patients without lipodystrophy. MAIN OUTCOME MEASURES: Body composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. RESULTS: PI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) x 10(-4) (min(-1)/microU/ml) versus 3.2 x 10(-4) and 4.6 x 10(-4) (min(-1)/microU/ml), respectively; P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass; P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. CONCLUSIONS: Body fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.

Adipose Tissue↗
PubMed2001

Dietary protein and weight reduction: a statement for healthcare professionals from the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association.

High-protein diets have recently been proposed as a "new" strategy for successful weight loss. However, variations of these diets have been popular since the 1960s. High-protein diets typically offer wide latitude in protein food choices, are restrictive in other food choices (mainly carbohydrates), and provide structured eating plans. They also often promote misconceptions about carbohydrates, insulin resistance, ketosis, and fat burning as mechanisms of action for weight loss. Although these diets may not be harmful for most healthy people for a short period of time, there are no long-term scientific studies to support their overall efficacy and safety. These diets are generally associated with higher intakes of total fat, saturated fat, and cholesterol because the protein is provided mainly by animal sources. In high-protein diets, weight loss is initially high due to fluid loss related to reduced carbohydrate intake, overall caloric restriction, and ketosis-induced appetite suppression. Beneficial effects on blood lipids and insulin resistance are due to the weight loss, not to the change in caloric composition. Promoters of high-protein diets promise successful results by encouraging high-protein food choices that are usually restricted in other diets, thus providing initial palatability, an attractive alternative to other weight-reduction diets that have not worked for a variety of reasons for most individuals. High-protein diets are not recommended because they restrict healthful foods that provide essential nutrients and do not provide the variety of foods needed to adequately meet nutritional needs. Individuals who follow these diets are therefore at risk for compromised vitamin and mineral intake, as well as potential cardiac, renal, bone, and liver abnormalities overall.

American Heart Association↗
PubMed2001

Occasional physical inactivity combined with a high-fat diet may be important in the development and maintenance of obesity in human subjects.

BACKGROUND: A better understanding of the environmental factors that contribute to obesity is imperative if any therapeutic effect on the increasing prevalence of overweight and obesity in the United States is to be achieved. OBJECTIVE: This study examined the effect of the interaction of diet composition and physical inactivity on energy and fat balances. DESIGN: Thirty-five normal-weight and obese subjects were randomly assigned to either a 15-d isoenergetic high-carbohydrate (HC) or high-fat (HF) diet according to a crossover design. During the first 14 d, body weight and physical activity were maintained. On day 15, subjects spent 23 h in a whole-room indirect calorimeter and were fed a diet similar to that consumed during the previous 7 d while remaining physically inactive. RESULTS: Energy intakes required to maintain body weight stability during the first 14 d were similar between diets. Normal-weight and obese subjects consuming both diets had a positive energy balance on the sedentary day (day 15), suggesting that subjects were less active in the calorimeter. There was no significant effect of diet composition on total energy balance and total protein-energy balance on day 15; however, carbohydrate balance was more positive with the HC (2497.8 +/- 301.2 kJ) than with the HF (1159 +/- 301.2 kJ) diet (P = 0.0032). Most importantly, fat balance was more positive with the HF (1790.8 +/- 510.4 kJ) than with the HC (-62.8 +/- 510.4 kJ) diet (P = 0.0011). CONCLUSION: Chronic consumption of a high-carbohydrate diet could provide some protection against body fat accumulation in persons with a pattern of physical activity that includes frequent sedentary days.

Adult↗
PubMed2001

Metabolic effects of rexinoids: tissue-specific regulation of lipoprotein lipase activity.

Hypertriglyceridemia is a frequent complication accompanying the treatment of patients with either retinoids or rexinoids, [retinoid X receptor (RXR)-selective retinoids]. To investigate the cellular and molecular basis for this observation, we have studied the effects of rexinoids on triglyceride metabolism in both normal and diabetic rodents. Administration of a rexinoid such as LG100268 (LG268) to normal or diabetic rats results in a rapid increase in serum triglyceride levels. LG268 has no effect on hepatic triglyceride production but suppresses post-heparin plasma lipoprotein lipase (LPL) activity suggesting that the hypertriglyceridemia results from diminished peripheral processing of plasma very low density lipoproteins particles. Treatment of diabetic rats with rexinoids suppresses skeletal and cardiac muscle but not adipose tissue LPL activity. This effect is independent of changes in LPL mRNA. In C2C12 myocytes, LG268 suppresses the level of cell surface (i.e., heparin-releasable) LPL activity without altering LPL mRNA. This effect is very rapid (t(1/2) = 2 h) and is blocked by the transcriptional inhibitor actinomycin D. These studies demonstrate that RXR ligands can have dramatic effects on the post-translational processing of LPL and suggest that skeletal muscle may be an important target of rexinoid action. In addition, these data underscore that the metabolic consequences of RXR activation are distinct from either retinoic acid receptor or peroxisome proliferator-activated receptor activation.

Animals↗
PubMed2001

A self-correcting indirect calorimeter system for the measurement of energy balance in small animals.

Indirect calorimetry involves measurement of CO(2) produced and O(2) consumed by an organism. These measurements are then used to calculate energy output, metabolic rate (MR), and respiratory quotient (RQ), a relative assessment of carbohydrate and lipid oxidation. By far the most difficult aspect of indirect calorimetry is measurement of O(2). Moreover, the abundance of O(2) (20.95%) relative to CO(2) (0.03%) in ambient conditions dictates that measurement errors of O(2) have greater implications on calculations of MR and RQ. Because compressed air is not feasible for use with animals in long-term experiments, changes in ambient conditions are nearly unavoidable. A self-correcting indirect calorimetry system was designed and constructed utilizing differential O(2) and CO(2) analyzers and a blank cage to monitor ambient conditions periodically. The system was validated by changing ambient O(2) and CO(2) concentrations by infusing N(2) into the system during a test butane burn. MR and RQ were largely unaffected by these changes in ambient conditions, and inclusion of a blank cage in the system accounted for slight calibration offsets. MR and RQ were measured in mice (n = 95) with and without correction for any small changes in ambient conditions measured in the blank cage. Coefficients of variation for MR and RQ were significantly decreased by taking into account ambient conditions measured in the blank cage (P < 0.001), which resulted in a 2.3% increase in precision for measurement of MR. This system will be used to more accurately assess long-term measurements of energy balance in the many murine models of leanness and obesity to gain better insights into pathophysiology and treatment of human obesity.

Animals↗
PubMed2001

Overexpressing human lipoprotein lipase in mouse skeletal muscle is associated with insulin resistance.

Lipoprotein lipase (LPL) plays a rate-limiting role in triglyceride-rich lipoprotein metabolism and is expressed in most tissues. Overexpression of LPL in skeletal muscle has been linked with higher plasma glucose levels suggesting insulin resistance (Jensen et al., Am J Physiol 273:R683-R689, 1997). The aim of our study was to ascertain whether the overexpression of human LPL in skeletal muscle leads to insulin resistance and to investigate the mechanism. Respiratory quotient measurements in both transgenic (MCKhLPL) and nontransgenic mice on a high-carbohydrate diet were conducted and showed a shift in fuel usage in transgenic mice when fasting but not when actively feeding. An increase in citrate and glucose 6-phosphate levels in fasted MCKhLPL mice further supports this preferential use of lipids. When challenged with an intraperitoneal injection of glucose (1 g/kg), MCKhLPL mice had a higher plasma glycemic excursion than nontransgenic mice. No differences in insulin response were observed between the two groups. Further investigation using hyperinsulinemic-euglycemic clamps revealed insulin resistance in MCKhLPL mice. Despite signs of insulin resistance, there was no associated increase in free fatty acids, hypertriglyceridemia, or hyperinsulinemia in MCKhLPL mice. In conclusion, MCKhLPL mice are insulin resistant, presumably due to increased delivery of lipoprotein-derived fatty acids to muscle.

Animals↗
PubMed2001

Maternal expression of functional lipoprotein lipase and effects on body fat mass and body condition scores of mature cats with lipoprotein lipase deficiency.

OBJECTIVE: To assess effects of deficiency of lipoprotein lipase (LPL) on body condition scores and lean and fat body masses of adult cats. ANIMALS: 12 cats without LPL mutations and 23 cats that were heterozygous or homozygous carriers of the Gly412Arg LPL mutation. PROCEDURE: Lean and fat body masses were estimated by use of body condition scores and change in enrichment of serum after IV administration of deuterium oxide. Mass spectroscopy and infrared absorbance methods were used to determine deuterium enrichment. RESULTS: Fat body mass (mean +/- SD; 0.2 +/- 0.1 kg) and percentage body fat (6.2 +/- 1.4%) of homozygotes were significantly less than those of clinically normal cats and heterozygotes (0.7 +/- 0.1 kg, 18.2 +/- 1.6% and 0.5 +/- 0.1 kg, 15.6 +/- 1.7%, respectively). Homozygous offspring of homozygous dams had significantly less fat body mass (0.1 +/- 0.1 kg) and percentage body fat (2.1 +/- 1.0%) than homozygous offspring of heterozygous dams (0.3 +/- 0.1 kg and 9.2 +/- 1.7%, respectively). Lean body mass did not differ significantly among groups. For all groups, percentage body fat was significantly correlated with body condition score (r= 0.65), and body condition scores supported findings for fat body mass. CONCLUSIONS AND CLINICAL RELEVANCE: Deficiency of LPL activity in cats diminishes stores of body fat. This is consistent with a low rate of de novo synthesis of fat. The effect of dam on body masses in mature LPL-deficient cats indicates nutrient programming of adipose formation during gestation or lactation.

Adipose Tissue↗
PubMed2001

A lipoprotein-containing particle is transferred from the serum across the mammary epithelium into the milk of lactating mice.

To investigate the role of low-density lipoprotein (LDL) in the delivery of cholesterol to the mammary gland during pregnancy and lactation, we examined the distribution of radioactivity from (125)I-tyramine cellobiose-LDL injected into the tail vein of female mice at various stages of the reproductive cycle. Changes in the proportion of isotope taken up by the mammary gland largely reflected the increased weight of the gland in pregnancy and lactation. In addition, during lactation, radioactivity was found in the milk and was associated with a protein of the molecular weight of apoB-100. Quantitatively similar results were obtained with mice homozygous for disruption of the LDL receptor gene (LDLR null). Analysis of endogenous lipoproteins showed that the milk lipoprotein particles were denser than the corresponding serum lipoproteins and largely depleted of triglyceride and cholesterol. Using fluorescence microscopy we visualize the sorting of apoB protein from the LDL lipid phase at the basal surface of the mammary epithelial cell of both wild-type and LDLR-null mice. Our findings provide evidence that the mammary epithelium of the lactating mouse is able to take up LDL from the plasma by a non-LDLR-mediated process. An apoB-containing particle from which the cholesterol has been removed is transferred into milk.

Animals↗