Increased Fat Stores Research Articles

Germline proliferation trades off with lipid metabolism in Drosophila.

Little is known about the metabolic basis of life-history trade-offs but lipid stores seem to play a pivotal role. During reproduction, an energetically highly costly process, animals mobilize fat reserves. Conversely, reduced or curtailed reproduction promotes lipid storage in many animals. Systemic signals from the gonad seem to be involved: Caenorhabditis elegans lacking germline stem cells display endocrine changes, have increased fat stores and are long-lived. Similarly, germline-ablated Drosophila melanogaster exhibit major somatic physiological changes, but whether and how germline loss affects lipid metabolism remains largely unclear. Here we show that germline-ablated flies have profoundly altered energy metabolism at the transcriptional level and store excess fat as compared to fertile flies. Germline activity thus constrains or represses fat accumulation, and this effect is conserved between flies and worms. More broadly, our findings confirm that lipids represent a major energetic currency in which costs of reproduction are paid.

Obesity, Sarcopenia and Myosteatosis: Impact on Clinical Outcomes in the Operative Management of Crohn's Disease.

Obesity, sarcopenia, and myosteatosis in inflammatory bowel disease may confer negative outcomes, but their prevalence and impact among patients with Crohn's disease (CD) have not been systematically studied. The aim of this study was to assess nutritional status and body composition among patients undergoing resectional surgery for CD and determine impact on operative outcomes. Consecutive patients with CD undergoing resection from 2000 to 2018 were studied. Total, subcutaneous, and visceral fat areas and lean tissue area (LTA) and intramuscular adipose tissue (IMAT) were determined preoperatively by computed tomography at L3 using SliceOmatic (Tomovision, Canada). Univariable and multivariable linear, logistic, and Cox proportional hazards regression were performed. One hundred twenty-four consecutive patients were studied (ileocolonic disease 53%, n = 62, biologic therapy 34.4% n = 43). Mean fat mass was 22.7 kg, with visceral obesity evident in 23.9% (n = 27). Increased fat stores were associated with reduced risk of emergency presentation but increased corticosteroid use (β 9.09, standard error 3.49; P = .011). Mean LBM was 9.9 kg. Sarcopenia and myosteatosis were associated with impaired baseline nutritional markers. Myosteatosis markers IMAT (P = .002) and muscle attenuation (P = .0003) were associated with increased grade of complication. On multivariable analysis, IMAT was independently associated with increased postoperative morbidity (odds ratio [OR], 1.08; 95% confidence interval (CI), 1.01-1.16; P = .037) and comprehensive complications index (P = .029). Measures of adiposity were not associated with overall morbidity; however, increased visceral fat area independently predicted venous thromboembolism (OR, 1.02; 95% CI, 1.00-1.05; P = .028), and TFA was associated with increased wound infection (OR, 1.00; 95% CI, 1.00-1.01; P = .042) on multivariable analysis. Myosteatosis is associated with nutritional impairment and predicts increased overall postoperative morbidity following resection for CD. Despite its association with specific increased postoperative risks, increased adiposity does not increase overall morbidity, reflecting preservation of nutritional status and relatively more quiescent disease phenotype. Impaired muscle mass and function represent an appealing target for patient optimization to improve outcomes in the surgical management of CD.

Migratory disposition alters lean mass dynamics and protein metabolism in migratory white-throated sparrows (Zonotrichia albicollis).

Migratory birds seasonally increase fat stores and the capacity to use fat to fuel long-distance migratory flights. However, lean mass loss also occurs during migratory flights and, if adaptive, should exhibit seasonal changes in the capacity for protein metabolism. We conducted a photoperiod manipulation using captive white-throated sparrows (Zonotrichia albicollis) to investigate seasonal changes in protein metabolism between the nonmigratory "winter" condition and after exposure to a long-day "spring" photoperiod to stimulate the migratory condition. After photostimulation, birds in the migratory condition rapidly increased fat mass and activity of fat catabolism enzymes. Meanwhile, total lean mass did not change, but birds increased the activity of protein catabolism enzymes and lost more water and lean mass during water-restricted metabolic testing. These data suggest that more protein may be catabolized during migratory seasons, corresponding with more water loss. Counter to predictions, birds in the migratory condition also showed an approximately 30-fold increase in muscle expression of sarcolipin, which binds to sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and uncouples Ca2+ transport from ATP hydrolysis. Our documented changes to protein catabolism enzymes and whole animal lean mass dynamics may indicate that protein breakdown or increased protein turnover is adaptive during migration in songbirds.

Secondary Malnutrition and Nutritional Intervention in Cholestatic Liver Diseases in Infants.

We aimed to conduct an updated review on the pathophysiology, diagnosis, and nutritional intervention of CCLD and secondary malnutrition in infants. Protein-energy malnutrition, impaired linear growth, fat-soluble vitamin deficiencies, and hepatic osteodystrophy can occur in up to 80% of cases. The proposed pathophysiological mechanisms include insufficient energy intake, lipid- and fat-soluble vitamin malabsorption, increased energy expenditure, altered intermediate metabolism, hormonal dysregulation, and systemic inflammation. The current approach to diagnosis is the identification of the deviation of growth parameters, body composition, and serum concentration of micronutrients, which determines the type and magnitude of malnutrition. Currently, liver transplantation is the best therapeutic alternative for the reversal of nutritional impairment. Early and effective portoenteroanatomosis can extend survival in patients with biliary atresia. Medical and dietary interventions in some storage and metabolic diseases can improve liver damage and thus the nutritional status. A proportion of patients with biliary atresia have fat-soluble vitamin deficiencies despite receiving these vitamins in a water-soluble form. With aggressive enteral nutrition, it may be possible to increase fat stores and preserve muscle mass and growth. The nutritional issues identified in the pre- and post-transplantation stages include muscle mass loss, bone demineralization, growth retardation, and obesity, which seems to correspond to the natural history of CCLD. Due to the implications for the growth and development of infants with CCLD with this complex malnutrition syndrome, innovative projects are required, such as the generation of prediction and risk models, biomarkers of growth and body composition, and effective strategies for nutritional prevention and intervention.

Body Mass Index and Saltwater Drowning.

Comparison of body mass index (BMI) was undertaken between 30 cases of salt water drowning and 30 age- and sex-matched controls randomly selected from the autopsy files of Forensic Science SA, Adelaide, Australia, during the period 2000 to 2017. The age range of drowning cases and controls was 18 to 80 (average, 49) years, with a male to female ratio of 19:11. The BMIs of the drowning cases ranged from 15.5 to 37.5 (average, 25.4; median, 23). The control cases had higher BMIs ranging from 22.9 to 44.3 (average, 29.2; median, 25). The number of obese (BMI, ≥30) decedents in the drowning group was 5 (17%) and in the controls was 9 (30%). Individuals who drown in the sea may regularly swim, and thus be fitter and therefore slimmer than more sedentary controls. However, it is also possible that greater amounts of adipose tissue may be protective against drowning, as increased fat stores could improve buoyancy. Thinner individuals with denser body mass may have to struggle more to avoid submersion. It could be that a low BMI is an underappreciated finding that may increase the risk of lethal immersion along with alcohol intoxication and poor swimming skills.

Severe Sarcopenia and Increased Fat Stores in Pediatric Patients With Liver, Kidney, or Intestine Failure.

Malnutrition and wasting predict clinical outcomes in children with severe chronic illness. Objectively calculated malnutrition in children with end-stage organ failure has not been well studied. This analysis compares children with kidney, liver or intestine failure to healthy controls to quantitate the disparity in muscle and fat stores. Children younger than 19 years with end-stage liver, kidney, or intestine failure and with pretransplant computed tomography (CT) imaging were selected from the transplant database. Age- and sex-matched healthy controls were selected from the trauma database. Measures of nutrition status included a scaled scoring of core muscle mass, and visceral and subcutaneous fat stores. Analysis was conducted using the pooled and individually matched subject-control differences. There were 81 subjects included in the final analysis (liver [n = 35], kidney [n = 20], and intestine [n = 26]). Children with end-stage liver disease had a 23% reduction in muscle mass, a 69% increase in visceral fat, and a 29% increase in subcutaneous fat. End-stage renal disease patients had a 19% reduction in muscle mass and a 258% increase in subcutaneous fat. Intestine failure patients had a 24% reduction in muscle mass, a 30% increase in visceral fat, and a 46% increase in subcutaneous fat. These results demonstrate significant sarcopenia and increased fat stores in end-stage organ failure patients, which supports the idea of an active physiologic mechanism to store fat while losing muscle mass. Sarcopenia may be related to total protein loss from a catabolic state, or from decreased synthesis (liver), wasting (kidney), or malabsorption (intestine).

Ubiquitin ligase RNF146 coordinates bone dynamics and energy metabolism.

Cleidocranial dysplasia (CCD) is an autosomal dominant human disorder characterized by abnormal bone development that is mainly due to defective intramembranous bone formation by osteoblasts. Here, we describe a mouse strain lacking the E3 ubiquitin ligase RNF146 that shows phenotypic similarities to CCD. Loss of RNF146 stabilized its substrate AXIN1, leading to impairment of WNT3a-induced β-catenin activation and reduced Fgf18 expression in osteoblasts. We show that FGF18 induces transcriptional coactivator with PDZ-binding motif (TAZ) expression, which is required for osteoblast proliferation and differentiation through transcriptional enhancer associate domain (TEAD) and runt-related transcription factor 2 (RUNX2) transcription factors, respectively. Finally, we demonstrate that adipogenesis is enhanced in Rnf146-/- mouse embryonic fibroblasts. Moreover, mice with loss of RNF146 within the osteoblast lineage had increased fat stores and were glucose intolerant with severe osteopenia because of defective osteoblastogenesis and subsequent impaired osteocalcin production. These findings indicate that RNF146 is required to coordinate β-catenin signaling within the osteoblast lineage during embryonic and postnatal bone development.

Distinct metabolic pathways trigger adipocyte fat accumulation induced by high-carbohydrate and high-fat diets

ObjectiveSeveral metabolic pathways may be associated with obesity development and may be differentially modulated by dietary constituents. The aim of this study was to access the adipocyte metabolic pathways that lead to lipid accumulation in fat cells of mice fed a high-carbohydrate or high-fat diet. MethodsMale Swiss mice ages 7 to 8 wk were fed a standard laboratory rodent diet—chow diet, a high-carbohydrate (HC) diet, or a high-fat (HF) diet for 8 wk. ResultsAnimals fed the HC diet exhibited a high lipogenesis rate and lipoprotein lipase activity even in a fasted state. Peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding proteins-1 mRNAs were increased in adipose tissue. The HF diet did not promote the lipogenic pathways but attenuated lipolytic activity and glucose uptake in adipocytes. ConclusionThe HC diet induces constitutive expression of lipogenic transcription factors during fasting, whereas the HF diet decreases lipolysis in adipocytes. Both pathways may contribute to increase fat stores and maintain an obese state.

Orexigenic Neuropeptide 26RFa: New Evidence for an Adaptive Profile of Appetite Regulation in Anorexia Nervosa

Restrictive anorexia nervosa (AN) presents an adaptive appetite regulating profile including mainly high levels of ghrelin. Because this adaptive mechanism is not effective on food intake, other appetite-regulating peptides need to be explored. 26RFa is a hypothalamic neuropeptide that stimulates appetite, gonadotropin release, and bone metabolism. The objective of the study was to evaluate the circadian levels of 26RFa in AN patients compared with healthy subjects, other eating disorders, and constitutional thinness (CT). This was a cross-sectional study performed in an endocrine unit and an academic laboratory. Five groups of age-matched young women were included in the study: 19 restrictive AN, 10 AN with bingeing/purging episodes, 14 with CT, 10 bulimic, and 10 normal-weight controls. Twelve-point circadian profiles of plasma 26RFa levels were measured in each subject. Significant circadian variations of 26 RFA were noticed in controls with higher values in the morning and abrupt decrease at noon. Twenty-four-hour mean 26RFa levels were significantly increased in restrictive AN and AN with bingeing/purging episodes (P < 0.001), predominantly in the afternoon and evening when compared with controls. Preprandial rises of 26 RFA were noticed in AN patients. Mean 26RFa levels trend to be higher in CT than in controls (P = 0.06) and significantly lower than in AN. The bulimic patients presented a circadian profile of 26RFa similar to that of controls. High levels of circulating 26RFa observed in AN patients might reflect an adaptive mechanism of the organism to promote energy intake and to increase fat stores in response to undernutrition.

Fructose, uricase, and the Back‐to‐Africa hypothesis

AbstractIn the Middle Miocene (approximately 17 to 12 Ma) at least two radiations of fossil apes from East Africa into Eurasia occurred, and, while controversial, some paleoanthropological studies suggest that one of the Eurasian lineages may have returned to Africa to evolve into humans and the African apes. Here, we present a novel argument supporting this hypothesis. Specifically, the global cooling that occurred in the middle Miocene rendered hominoids living in Europe at risk for starvation as seasonal climate change resulted in less availability of fruits during the winter months. During this time, a mutation in uricase occurred in early hominids that resulted in a rise in serum uric acid. Uric acid has been found to potentiate the effect of fructose to increase fat stores, suggesting that the mutation provided a survival advantage. Such a survival advantage would have been less likely to occur in Africa, where the continued presence of tropical rainforests would have been more likely to provide food throughout the year. Furthermore, Miocene apes in Europe were in protected sites where geographic isolation could have allowed the uricase mutation to be rapidly expressed in the entire population. While speculative, we suggest that the uricase mutation supports an extra‐Africa origin of humans.

De Novo Lipogenesis and Stearoyl-CoA Desaturase Are Coordinately Regulated in the Human Adipocyte and Protect against Palmitate-induced Cell Injury

De novo lipogenesis (DNL) is paradoxically up-regulated by its end product, saturated fatty acids (SAFAs). We tested the hypothesis that SAFA-induced up-regulation of DNL reflects coordinate up-regulation of elongation and desaturation pathways for disposal of SAFAs and production of monounsaturated fatty acids to protect cells from SAFA toxicity. Human preadipocytes were differentiated in vitro for 14 days with [U-(13)C]palmitate (0-200 microM) to distinguish exogenous fatty acids from those synthesized by DNL. Exogenous palmitate up-regulated DNL (p < 0.001) concomitantly with SCD and elongation (each p < 0.001). Adipocytes from some donors were intolerant to high palmitate concentrations (400 microM). Palmitate-intolerant cells showed lower TG accumulation. They had lower expression of SCD mRNA and less monounsaturated fatty acids in TG, emphasizing the importance of desaturation for dealing with exogenous SAFAs. There was greater [U-(13)C]palmitate incorporation in phospholipids. SCD knockdown with small interfering RNA caused down-regulation of DNL and of expression of DNL-related genes, with reduced membrane fluidity (p < 0.02) and insulin sensitivity (p < 0.01), compared with scrambled small interfering RNA controls. There was preferential channeling of DNL-derived versus exogenous palmitate into elongation and of DNL-derived versus exogenous stearate into desaturation. DNL may not act primarily to increase fat stores but may serve as a key regulator, in tandem with elongation and desaturation, to maintain cell membrane fluidity and insulin sensitivity within the human adipocyte.

Factors that may impede the weight loss response to exercise‐based interventions

The results of exercise programmes designed to reduce body fat are disappointing. However, the reporting of weight loss as mean values disguises those individuals who do lose significant amounts of fat. Why some participants produce significant exercise-induced fat loss whereas others lose little or increase fat stores is likely to be an outcome of a range of behavioural (e.g. sleep deprivation, caloric intake), inherited (e.g. muscle fibre type, gender) and physiological (e.g. hyperinsulinaemia, hypothyroidism) factors. The following review highlights possible factors involved in weight loss and discusses how individual differences may determine the extent of weight loss after an exercise intervention. Finally, implications for the treatment and prevention of obesity are discussed.

Catecholamine-induced lipolysis in adipose tissue and skeletal muscle in obesity

Increased fat storage in adipose and non-adipose tissue (e.g. skeletal muscle) characterizes the obese insulin resistant state. Disturbances in pathways of lipolysis may play a role in the development and maintenance of these increased fat stores. A reduced catecholamine-induced lipolysis may contribute to the development and maintenance of increased adipose tissue stores. To data, a reduced hormone-sensitive lipase (HSL) expression is the best characterized defect contributing to this catecholamine resistance. The recently discovered adipose triglyceride lipase (ATGL) seems not to be involved in the catecholamine resistance of lipolysis observed in abdominal subcutaneous adipose tissue of obese subjects, which contrasts with findings in mice studies. So far, little is known on the regulation of skeletal muscle lipolysis. There is evidence of both HSL and ATGL activity and/or expression in skeletal muscle. A blunted fasting and/or catecholamine-induced lipolysis has been reported in skeletal muscle, but data require confirmation. It is tempting to speculate that an imbalance between ATGL and HSL expression results in incomplete lipolysis and increased accumulation of lipid intermediates in skeletal muscle of obese insulin resistant subjects. The latter may inhibit insulin signalling and play a role in the development of type 2 diabetes. This review summarizes the current knowledge on (intracellular) adipose tissue and skeletal muscle lipolysis in obesity, discusses the underlying mechanisms of these disturbances and will finally address the question whether disturbances in the lipolytic pathways may be primary factors in the etiology of obesity or adaptational responses to the obese insulin resistant state.

Metabolic homeostasis and tissue renewal are dependent on β1,6GlcNAc-branched N-glycans

Golgi beta1,6-N-acetylglucosaminyltransferase V (Mgat5) produces beta1,6GlcNAc-branched N-glycans on glycoproteins, which increases their affinity for galectins and opposes loss from the cell surface to constitutive endocytosis. Oncogenic transformation increases Mgat5 expression, increases beta1,6GlcNAc-branched N-glycans on epidermal growth factor and transforming growth factor-beta receptors, and enhances sensitivities to ligands, cell motility, and tumor metastasis. Here, we demonstrate that Mgat5(-/-) mouse embryonic fibroblasts (MEFs) display reduced sensitivity to anabolic cytokines and reduced glucose uptake and proliferation. Mgat5(-/-) mice are also hypoglycemic, resistant to weight gain on a calorie-enriched diet, hypersensitive to fasting, and display increased oxidative respiration and reduced fecundity. Serum-dependent activation of the extracellular response kinase (growth) and Smad2/3 (arrest) pathways in Mgat5(-/-) MEFs and bone marrow cells reveals an imbalance favoring arrest. Mgat5(-/-) mice have fewer muscle satellite cells, less osteogenic activity in bone marrow, and accelerated loss of muscle and bone mass with aging. Our results suggest that beta1,6GlcNAc-branched N-glycans promote sensitivity to anabolic cytokines, and increase fat stores, tissue renewal, and longevity.

A reciprocal interaction between food-motivated behavior and diet-induced obesity

One of the main causes of obesity is overconsumption of diets high in fat and sugar. We studied the metabolic changes and food-motivated behavior when rats were subjected to a choice diet with chow, lard and a 30% sucrose solution (high fat high sugar (HFHS)-choice diet). Because rats showed considerable variations in the feeding response to HFHS-choice diet and in food-motivated behavior, we investigated whether the motivation to obtain a sucrose reward correlated with the development of obesity when rats were subsequently subjected to HFHS-choice diet. We first studied feeding, locomotor activity and body temperature, fat weights and hormonal concentrations when male Wistar rats were subjected to HFHS-choice diet for 1 week. Second, we studied sucrose-motivated behavior, using a progressive ratio (PR) schedule of reinforcement in rats that were subjected to the HFHS-choice diet for at least 2 weeks, compared to control rats on a chow diet. Third, we measured motivation for sucrose under a PR schedule of reinforcement in rats that were subsequently subjected to HFHS-choice diet or a chow diet for 4 weeks. Fat weights were measured and correlated with the motivation to obtain sucrose pellets. One week on the HFHS-choice diet increased plasma concentrations of glucose and leptin, increased fat stores, but did not alter body temperature or locomotor activity. Moreover, consuming the HFHS-choice diet for several weeks increased the motivation to work for sucrose pellets. Furthermore, the motivation to obtain sucrose pellets correlated positively with abdominal fat stores in rats subsequently subjected to the HFHS-choice diet, whereas this correlation was not found in rats fed on a chow diet. Our data suggest that the motivation to respond for palatable food correlates with obesity due to an obesogenic environment. Conversely, the HFHS-choice diet, which results in obesity, also increased the motivation to work for sucrose. Thus, being motivated to work for sucrose results in obesity, which, in turn, increases food-motivated behavior, resulting in a vicious circle of food motivation and obesity.

Seasonality, division of labor, and dynamics of colony-level nutrient storage in the ant Pheidole morrisi

Nutritional provisioning is a critical component of life history strategies, and of particular interest in social insect colonies because of the role that division of labor plays in resource allocation. To explore the mechanisms that underlie colony nutritional strategies, I examined three populations of the ant Pheidole morrisi across a gradient of overwinter food scarcity over two seasons. P. morrisi colonies were found to employ amixed strategy of fat storage with regard to a longer overwinter period: members of both worker castes increase their percent-fat in a graded manner, while the proportion of a specialized subcaste of majors known as “repletes”, also increased within the colony. Geographic variation in other colony traits such as mean colony size, mean worker size, and minor/major caste ratio were also found, although not always in a manner clearly relating to fat storage. These results indicate that colony demography responds to seasonal fluctuations in food availability through behavioral alterations (increased fat stores and recruitment of replete workers) rather than physical alterations (changes in lean body sizes or caste ratio). The findings illustrate the dynamic role division of labor plays in the success of insect colonies confronting environmental variability.

Medical consequences of obesity.

Obesity is an epidemic disease that threatens to inundate health care resources by increasing the incidence of diabetes, heart disease, hypertension, and cancer. These effects of obesity result from two factors: the increased mass of adipose tissue and the increased secretion of pathogenetic products from enlarged fat cells. This concept of the pathogenesis of obesity as a disease allows an easy division of disadvantages of obesity into those produced by the mass of fat and those produced by the metabolic effects of fat cells. In the former category are the social disabilities resulting from the stigma associated with obesity, sleep apnea that results in part from increased parapharyngeal fat deposits, and osteoarthritis resulting from the wear and tear on joints from carrying an increased mass of fat. The second category includes the metabolic factors associated with distant effects of products released from enlarged fat cells. The insulin-resistant state that is so common in obesity probably reflects the effects of increased release of fatty acids from fat cells that are then stored in the liver or muscle. When the secretory capacity of the pancreas is overwhelmed by battling insulin resistance, diabetes develops. The strong association of increased fat, especially visceral fat, with diabetes makes this consequence particularly ominous for health care costs. The release of cytokines, particularly IL-6, from the fat cell may stimulate the proinflammatory state that characterizes obesity. The increased secretion of prothrombin activator inhibitor-1 from fat cells may play a role in the procoagulant state of obesity and, along with changes in endothelial function, may be responsible for the increased risk of cardiovascular disease and hypertension. For cancer, the production of estrogens by the enlarged stromal mass plays a role in the risk for breast cancer. Increased cytokine release may play a role in other forms of proliferative growth. The combined effect of these pathogenetic consequences of increased fat stores is an increased risk of shortened life expectancy.

Difference in Migration Pattern Between Adult and Immature Birds Using Satellites

Abstract We satellite-tracked Steller's Sea Eagles (Haliaeetus pelagicus), Black-faced Spoonbills (Platalea minor), and White-naped Cranes (Grus vipio) to determine migration routes and stopover tactics of adult and immature birds. During spring migration, there were no significant differences between adult and immature birds in total migration distance and distance between stopover sites, but the migration period and resting period at stopover sites were significantly longer in immature individuals. There are two possible tactics for migrating without expending fat stores: longer rests or shorter migration distances between stopover sites. Our results suggest that immature birds try to increase fat stores by increasing time available for foraging at stopover sites.

Difference in Migration Pattern Between Adult and Immature Birds Using Satellites

Abstract We satellite-tracked Steller's Sea Eagles (Haliaeetus pelagicus), Black-faced Spoonbills (Platalea minor), and White-naped Cranes (Grus vipio) to determine migration routes and stopover tactics of adult and immature birds. During spring migration, there were no significant differences between adult and immature birds in total migration distance and distance between stopover sites, but the migration period and resting period at stopover sites were significantly longer in immature individuals. There are two possible tactics for migrating without expending fat stores: longer rests or shorter migration distances between stopover sites. Our results suggest that immature birds try to increase fat stores by increasing time available for foraging at stopover sites.

A PRELIMINARY STUDY OF CARDIOVASCULAR RISK BEHAVIORS IN ADOLESCENT TRANSPLANT PATIENTS

690 After transplantation, many adolescents experience significant weight gain coupled with poor physical activity. These changes are generally believed to be related to the improved feeling of well being, increased appetite, and altered metabolism associated with immunosuppressive drugs and transplantation. Since renal transplant recipients' life expectancies are increasing, long term risk factors for cardiovascular disease must be addressed. To deter risk factors and help encourage compliance, an educational program including diet, medication, and risk behaviors was instituted at the time of transplantation and twice yearly thereafter. The primary purpose of this study was to determine the effectiveness of the current education program. Patients (24) receiving care at the University of Alabama at Birmingham were enrolled: median 17 months post-transplant (range 1-152), 75% male/25% female, 58% white/42% black, median age 17 years (range 13-23). Anthropo-metric data demonstrated 67% of subjects with moderate to severe growth retardation, 72% were overweight to morbidly obese (based on percent ideal body weight and body mass index), triceps skinfolds showed that 82% were obese with mildly to severely increased fat stores, mid-arm muscle circumferences indicated that 88% had mild to severe muscle wasting and protein depletion. Other data related to cardiovascular risk factors (blood pressure, lipid levels) were evaluated: 86% of subjects had significantly elevated BP, 50% had elevated cholesterol, 40% had elevated triglycerides, and 40% had elevated LDL-C and VLDL-C. Significant correlations were noted between cyclosporine levels and total cholesterol and LDL-C. To determine patient behaviors, subjects completed the Youth Risk Behavior Survey and were found to be significantly less physically active than the reference YRBSS students. To determine dietary intake, subjects completed a 3 day diet diary and 24 hour diet recall. In spite of diet education, 28% of the subjects responded that they were on no special diet, and only 5.6% described the prescribed diet regimen. Though approximately 72% were considered to be obese, 78% were below Recommended Dietary Allowances for calories. This suggests the diet records were not reliable predictors of actual intake. These data suggest that the majority of these patients are obese with a high percentage of their body composition as fat, have significantly elevated lipid levels, poorly controlled hypertension, and decreased physical activity. All of these have been demonstrated to increase their risk for cardiovascular disease. Clearly new approaches to patient care and education are needed.