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Biomedical subjects

Walter J Pories

Publications and source records attributed to Walter J Pories.

At least 19 recordsLinked to original sources
PubMed2006

Expression of genes regulating malonyl-CoA in human skeletal muscle.

In humans and animal models, increased intramuscular lipid (IML) stores have been implicated in insulin resistance. Malonyl-CoA plays a critical role in cellular lipid metabolism both by serving as a precursor in the synthesis of lipids and by inhibiting lipid oxidation. In muscle, Malonyl-CoA acts primarily as a negative allosteric regulator of carnitine palmitoyl transferase-1 (CPT1) activity, thereby blocking the transport of long chain fatty acyl CoAs into the mitochondria for oxidation. In muscle, increased malonyl-CoA, decreased muscle CPT1 activity, and increased IML have all been reported in obesity. In order to determine whether malonyl-CoA synthesis might be under transcriptional as well as biochemical regulation, we measured mRNA content of several key genes that contribute to the cellular metabolism of malonyl-CoA in muscle biopsies from lean to morbidly obese subjects. Employing quantitative real-time PCR, we determined that expression of mitochondrial acetyl-CoA carboxylase 2 (ACC2) was increased by 50% with obesity (P < 0.05). In both lean and obese subjects, expression of mitochondrial ACC2 was 20-fold greater than that of cytoplasmic ACC1, consistent with their hypothesized roles in synthesizing malonyl-CoA from acetyl-CoA for CPT1 regulation and lipogenesis, respectively. In addition, in both lean and obese subjects, expression of malonyl-CoA decarboxylase was approximately 40-fold greater than fatty acid synthase, consistent with degradation, rather than lipogenesis, being the primary fate of malonyl-CoA in human muscle. No other genes showed signs of increased mRNA content with obesity, suggesting that there may be selective transcriptional regulation of malonyl-CoA metabolism in human obesity.

Acetyl-CoA Carboxylase↗
PubMed2005

Suppression of hepatic cholesteryl ester transfer protein expression in obese humans with the development of type 2 diabetes mellitus.

Cholesteryl ester transfer protein (CETP) is a plasma enzyme that can modulate the profile of lipoproteins and is thus considered: 1) a mediator of vascular disease; and 2) a therapeutic target for vascular disease. In the present study, we pursued a better understanding of the effect of type 2 diabetes on the expression of CETP in obese patients. Obesity was accompanied by a 20% elevation in plasma CETP that was eliminated with the development of diabetes. These differences were observed for both men and women and were due to variations in the amount of CETP protein in the plasma. The mRNA and protein of both the full-length (CETPFL) and alternatively spliced (CETPDelta9) forms of CETP were lower in the liver, but not in either sc or omental adipose tissue depots, of diabetic obese subjects. Sterol response element binding proteins 1 and 2 were also lower in liver homogenates, suggesting that these transcription factors may mediate the effects of type 2 diabetes on hepatic CETP expression. Thus, the suppressive effects of type 2 diabetes in obese subjects are observed in both men and women and may be due, at least in part, to a suppression of hepatic CETP expression.

Adult↗
PubMed2005

Epidemiology of obesity in the United States.

The challenges of the epidemic are not limited to concerns about bulk and weight. The disabilities caused by obesity are physiologic and psychosocial. The increased waist to hip girth is associated with increased risk of cardiovascular disease, hyperlipidemia, hypertension, and diabetes. Obesity also has been related directly to increased risk of sleep apnea, cancer, gallbladder disease, musculoskeletal disorders, severe pancreatitis, bacterial panniculitis, diverticulitis, infertility, urinary incontinence, and idiopathic intracranial hypertension. The psychosocial factors and quality of life in the obese population also have been documented. Although there is some debate, the obese have been found to be twice as likely to suffer from anxiety, impaired social interaction,and depression when compared with the nonobese population. Although advances in obesity surgery have resulted in long-term, lasting treatment of this disease and some of its comorbidities (ie, diabetes, hypertension, sleep apnea), There is a pressing need to develop a comprehensive medical and nutrition plan to reduce the prevalence of this newly identified disease state. Some draw parallels to tobacco and the morbidity and mortality associated with its use. Perhaps there are similarities in these two epidemics. Both start with education of the population as to the morbidities and mortality associated with the disease. As with tobacco, this education is especially important for youth. Without a plan of education to promote nutrition and increased physical activity, and continued research into the causes of obesity, the prevalence of obesity will continue to rise in the United States.

Adolescent↗
PubMed2005

Endothelial nitric oxide synthase content in adipose tissue from obese and lean African American and white American women.

It has been demonstrated that the enzyme endothelial nitric oxide synthase (eNOS) is present in adipose tissue, resulting in nitric oxide production and subsequent inhibition of lipolysis. A higher eNOS content has also been reported in the subcutaneous abdominal adipose tissue of obese than in that of lean white men. Furthermore, a lower lipolytic rate in obese than in lean women and a lower lipolytic rate in African American (AA) than in white American (WA) women have been demonstrated. The purpose of this study was to determine if eNOS protein content is higher in the subcutaneous and omental adipose tissues of obese than in those of lean women and if eNOS protein content is higher in the subcutaneous and omental adipose tissues of AA than in those of WA women. Whole tissue homogenates were prepared from frozen omental and subcutaneous adipose tissue samples obtained from lean and obese and AA and WA elective abdominal surgery patients and were analyzed for eNOS protein content using enzyme-linked immunosorbent assay. The adipose tissue eNOS protein content was approximately 40% higher in obese than in lean individuals (omental, 326.9 +/- 40.5 pg/mL lean and 445.3 +/- 38.0 pg/mL obese; subcutaneous, 246.8 +/- 20.8 pg/mL lean and 343.1 +/- 19.0 pg/mL obese; P < .05). There was no difference between the races for eNOS protein content in omental adipose tissue. In subcutaneous adipose tissue, there was a higher eNOS content in obese (417.1 +/- 78.9 pg/mg total protein) than in lean (216.7 +/- 29.9 pg/mg total protein) (P < .05) WA women, but there was no difference in subcutaneous adipose eNOS content between obese and lean AA women (250.7 +/- 47.4 and 294.1 +/- 42.2 pg/mg total protein, respectively). The higher eNOS content in the adipose tissue of obese than in that of lean WA women in the fasted state may contribute to the reduced lipolytic activity in WA women; however, eNOS protein content probably does not contribute to differences in lipolytic rates between AA and WA women.

Adipose Tissue↗
PubMed2005

Quality assurance in bariatric surgery.

Quality assurance is a function that exists in manufacturing,engineering, and the service industry. Bariatric surgery is an undertaking with a special form of consumer product and service. In this day of limited resources and significant value exchanges among stakeholders (ie, patients, surgeons, third-party payers),the goal of the bariatric community is to deliver quality outcomes with safety, efficacy, and efficiency. The American Society for Bariatric Surgery and the Surgical Review Corporation, in conjunction with the bariatric community, will use quality assurance methods to produce quality outcomes that will satisfy the value exchanges of all stakeholders.

Gastric Bypass↗
PubMed2004

Ethnic differences in adiponectin levels.

Adiponectin levels were measured in African American and Caucasian women of varying body mass index (BMI). Plasma adiponectin levels were compared and the relationship between adiponectin and insulin sensitivity was assessed. Adiponectin levels were similar in the Caucasian obese (7.0 +/- 0.8 microg/mL), African American obese (7.3 +/- 3.5 microg/mL), and African American non-obese women (7.1 +/- 1.2 microg/mL), but were significantly higher in Caucasian non-obese women (12.2 +/- 1.4 microg/mL). Correlational analyses demonstrated that BMI, insulin, and homeostasis model assessment (HOMA) correlated significantly with adiponectin levels in only the Caucasian women. These results provide support for the notion that what applies to other ethnic populations might not apply to the African American population, and that the association between adiponectin and insulin sensitivity needs to be clarified in the African American population.

Adiponectin↗
PubMed2003

Fatty acid oxidation by skeletal muscle homogenates from morbidly obese black and white American women.

The purpose of this study was to determine if there were differences in the capacity of skeletal muscle from morbidly obese Black and White American women to oxidize fatty acids. The oxidation rates of (14)C-palmitate, (14)C-palmitoyl-CoA, and (14)C-palmitoyl-carnitine were measured in whole homogenates of rectus abdominus from Black and White women who were similar in age and body mass index (BMI). The activities of muscle citrate synthase (CS), beta-hydroxy acyl-CoA dehydrogenase (beta-HAD), and mitochondrial and microsomal acyl-CoA synthetase (ACS) were measured in the 2 groups. The results showed that the rate of (14)C-palmitate oxidation by muscle of Black women was 25% that of Whites (8.7 +/- 1.5 v 34.4 +/- 6.8 nmol (14)CO(2) produced/gram tissue wet weight/ hour; P <.05), but the rates of (14)C-palmitoyl-CoA and (14)C-palmitoyl-carnitine oxidation were not different in the 2 groups. No differences were found in the activities of CS or beta-HAD. However, the activities of both mitochondrial and microsomal ACS were lower in the Black women than the Whites (mitochondrial ACS 25.1 +/- 3.9 v 36.4 +/- 5.0 nmol/mg protein/min; P <.05; microsomal ACS 6.2 +/- 0.5 v 8.5 +/- 0.5; nmol/mg protein/min; P <.005). The lower rate of palmitate oxidation, and the lack of differences in the rates of palmitoyl-CoA and palmitoyl-carnitine oxidation indicate that there is a defect in the activation of the fatty acid in the muscle of the Black women. This was confirmed by the decrease in mitochondrial ACS activity in the Black women. The decreased fatty acid oxidation by skeletal muscle of obese Black women could result in shunting these fuels from muscle to adipose tissue for storage, which may contribute to the maintenance of obesity in the Black women.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed2003

Appropriateness of quality indicators for older patients with advanced dementia and poor prognosis.

OBJECTIVES: To evaluate the applicability of process-of-care quality indicators (QIs) to vulnerable elders and to measure the effect of excluding indicators based on patients' preferences and for advanced dementia and poor prognosis. DESIGN: The Assessing Care of Vulnerable Elders (ACOVE) project employed 203 QIs for care of 22 conditions (including six geriatric syndromes and 11 age-associated diseases) for community-based persons aged 65 and older at increased risk of functional decline or death. Relevant QIs were excluded for persons deciding against hospitalization or surgery. A 12-member clinical committee (CC) of geriatric experts rated whether each QI should be applied in scoring quality of care for persons with advanced dementia (AdvDem) or poor prognosis (PoorProg). Using content analysis, CC ratings were formulated into a model of QI exclusion. Quality scores with and without excluded QIs were compared. SETTING: Enrollees in two senior managed care plans, one in the northeast United States and the other in the southwest. PARTICIPANTS: CC members evaluated applicability of QIs. QIs were applied to 372 vulnerable elders in two senior managed care plans. MEASUREMENTS: Frequency and type of QIs excluded and the effect of excluding QIs on quality of care scores. RESULTS: Of the 203 QIs, a patient's preference against hospitalization or surgery excluded 10 and eight QIs, respectively. The CC voted to exclude 81.5 QIs (40%) for patients with AdvDem and 70 QIs (34%) for patients with PoorProg. Content analysis of the CC votes revealed that QIs aimed at care coordination, safety or prevention of decline, or short-term clinical improvement or prevention with nonburdensome interventions were usually voted for inclusion (90% and 98% included for AdvDem and PoorProg, respectively), but QIs directed at long-term benefit or requiring interventions of moderate to heavy burden were usually excluded (16% and 19% included, respectively). About half of QIs aimed at age-associated diseases were voted for exclusion, whereas fewer than one-quarter of QIs for geriatric syndromes were excluded. Thirty-nine patients (10%) in our field trial held preferences or had clinical conditions that would have excluded 68 QIs. This accounted for 5% of all QIs triggered by these 39 patients and 0.6% of QIs overall. The quality score without exclusion was 0.57 and with exclusion was 0.58 (P =.89). CONCLUSION: Caution is required in applying QIs to vulnerable elders. QIs for geriatric syndromes are more likely to be applicable to these individuals than are QIs for age-associated diseases. The objectives of care, intervention burdens, and interval before anticipated benefit affect QI applicability. At least for patients with AdvDem and PoorProg, identification of applicable or inapplicable QIs is feasible. In a community-based sample of vulnerable elders, few QIs are excluded.

Aged↗
PubMed2003

Current status and future directions of geriatric general surgery.

As the population ages and requires more health care, a significant part of this is in surgical services. As elderly patients account for a growing proportion of most surgeons' practices, it is apparent that this patient group has special requirements, differences in outcomes, and different physiology from other patients encountered in the typical surgical practice. The greater frequency of emergency operations in older than in younger patients, with higher morbidity and mortality rates, compounds these differences. This paper reviews the current status of general surgery in older patients with a special focus on emergency procedures, major abdominal surgery, biliary disease, endocrine disease, and breast cancer. Each of these areas is a source of considerable interest to general surgeons.

Aged↗
PubMed2002

Skeletal muscle lipid metabolism with obesity.

The objectives of this study were to 1). examine skeletal muscle fatty acid oxidation in individuals with varying degrees of adiposity and 2). determine the relationship between skeletal muscle fatty acid oxidation and the accumulation of long-chain fatty acyl-CoAs. Muscle was obtained from normal-weight [n = 8; body mass index (BMI) 23.8 +/- 0.58 kg/m(2)], overweight/obese (n = 8; BMI 30.2 +/- 0.81 kg/m(2)), and extremely obese (n = 8; BMI 53.8 +/- 3.5 kg/m(2)) females undergoing abdominal surgery. Skeletal muscle fatty acid oxidation was assessed in intact muscle strips. Long-chain fatty acyl-CoA concentrations were measured in a separate portion of the same muscle tissue in which fatty acid oxidation was determined. Palmitate oxidation was 58 and 83% lower in skeletal muscle from extremely obese (44.9 +/- 5.2 nmol x g(-1) x h(-1)) patients compared with normal-weight (71.0 +/- 5.0 nmol x g(-1) x h(-1)) and overweight/obese (82.2 +/- 8.7 nmol x g(-1) x h(-1)) patients, respectively. Palmitate oxidation was negatively (R = -0.44, P = 0.003) associated with BMI. Long-chain fatty acyl-CoA content was higher in both the overweight/obese and extremely obese patients compared with normal-weight patients, despite significantly lower fatty acid oxidation only in the extremely obese. No associations were observed between long-chain fatty acyl-CoA content and palmitate oxidation. These data suggest that there is a defect in skeletal muscle fatty acid oxidation with extreme obesity but not overweight/obesity and that the accumulation of intramyocellular long-chain fatty acyl-CoAs is not solely a result of reduced fatty acid oxidation.

Acyl Coenzyme A↗
PubMed2002

Effect of weight loss on muscle lipid content in morbidly obese subjects.

The purpose of this study was to test the hypothesis that weight loss results in a reduction in intramuscular lipid (IMCL) content that is concomitant with enhanced insulin action. Muscle biopsies were obtained from morbidly obese individuals [body mass index (BMI) 52.2 +/- 2.5 kg/m(2); n = 6] before and after gastric bypass surgery, an intervention that improves insulin action. With intervention, there was a 47% reduction (P < 0.01) in BMI and a 93% decrease in homeostasis model assessment, or HOMA (7.0 +/- 1.9 vs. 0.5 +/- 0.1). Histochemically determined IMCL content decreased (P < 0.05) by approximately 30%. In relation to fiber type, IMCL was significantly higher in type I vs. type II fibers. In both fiber types, there were reductions in IMCL and trends for muscle atrophy. Despite these two negating factors, the IMCL-to-fiber area ratio still decreased by approximately 44% with weight loss. In conclusion, despite differing initial levels and possible atrophy, weight loss appears to decrease IMCL deposition to a similar relative extent in type I and II muscle fibers. This reduction in intramuscular triglyceride may contribute to enhanced insulin action seen with weight loss.

Adipose Tissue↗