Search PubMed⌕ Search

Biomedical subjects

M D Jensen

Publications and source records attributed to M D Jensen.

At least 55 records · Page 3Linked to original sources
PubMed1999

Relationship between urinary albumin excretion, body composition, and hyperinsulinemia in normotensive glucose-tolerant adults.

OBJECTIVE: Elevated urinary albumin excretion (UAE) has been associated with insulin resistance and is suggested to be elevated in prediabetic individuals. Upper body obesity, especially visceral obesity, predicts insulin resistance and development of type 2 diabetes. We examined whether UAE clusters with obesity-associated insulin resistance traits in healthy glucose-tolerant normotensive subjects. RESEARCH DESIGN AND METHODS: There were 49 volunteers with a wide range of body fat and body fat distribution studied. All had normal blood pressure and glucose tolerance and were maintained on a controlled diet for 2 weeks. UAE was assessed from three overnight urine collections, and body composition was assessed by whole-body dual-energy X-ray absorptiometry scanning and abdominal computed tomography scanning. RESULTS: Fasting insulin and insulin responses to oral glucose were significantly increased in obese subjects, who also tended to have more dyslipidemia, greater blood pressure, and more visceral fat than lean subjects. These differences were more apparent in upper body obese subjects. UAE was normal in obese and upper body obese subjects and not different from that of lean subjects. UAE ranged from 0.3 to 8.3 micrograms/min in lean subjects and from 0.2 to 7.2 micrograms/min in obese subjects. UAE was not significantly correlated with body composition, plasma insulin, glucose, or lipids. CONCLUSIONS: Obese subjects (even upper body obese subjects) with increased visceral and total body fat, high plasma insulin and triglycerides, and low HDL cholesterol concentrations do not have elevated UAE. This suggests that UAE is not closely associated with these characteristics and implies a later onset of abnormal albuminuria in the course of the insulin resistance syndrome.

Adipose Tissue↗
PubMed1999

Echocardiographic improvement over time after cessation of use of fenfluramine and phentermine.

OBJECTIVE: To determine the echocardiographic changes over time of valvular heart lesions in patients who took the weight loss drugs fenfluramine and phentermine. SUBJECTS AND METHODS: This prospective cohort study began at the termination of a randomized, double-blind, placebo-controlled weight loss trial of 18 obese women and 13 obese men (mean age, 42 years; mean body mass index, 33.4 kg/m2) who had been assigned randomly to treatment with fenfluramine and phentermine or to placebo. Echocardiograms were obtained at termination of the trial when fenfluramine was withdrawn from the market and 6 months later. They were interpreted independently by 3 cardiologists blinded to treatment assignment and temporal sequence of the echocardiograms. The main outcome measure was the change in drug-related valvular disease over time. RESULTS: One subject assigned to receive the drugs was lost to follow-up, and 3 subjects who did not meet a weight loss goal of 10 kg crossed over from placebo to drug treatment. Echocardiograms were obtained in 19 subjects who received the drugs and 11 subjects who received placebo, and 6-month follow-up echocardiograms were obtained in 15 subjects who received the drugs and 3 who received placebo. Subjects had taken fenfluramine and phentermine a mean of 41 weeks (range, 8-73 weeks). Five of 19 subjects who received the drugs (26%; 95% confidence interval, 7%-46%) and 1 of 11 who received placebo (9%) (odds ratio, 3.6; 95% confidence interval, 0.4-35.6) had findings that met criteria established for drug-related valvular disease. All 5 subjects (4 women and 1 man) receiving the drugs had mild aortic regurgitation, and 1 also had pulmonary hypertension (estimated pulmonary artery pressure, 59 mm Hg). Six months later, the echocardiographic findings had improved in all 5 subjects (P=.06), and 3 no longer met the criteria for drug-related valvular disease. Pulmonary artery pressures decreased to near normal in the subject with pulmonary hypertension (37 mm Hg). Overall, the echocardiographic valvular features improved in 8 of 15 subjects who received the drugs and had echocardiograms performed at both time periods (P=.008). CONCLUSIONS: Valvular heart disease did not appear to progress after cessation of use of fenfluramine and phentermine, and echocardiographic valvular features appeared to improve over time.

Adrenergic Agents↗
PubMed1998

Adipocyte macrophage colony-stimulating factor is a mediator of adipose tissue growth.

Adipose tissue growth results from de novo adipocyte recruitment (hyperplasia) and increased size of preexisting adipocytes. Adipocyte hyperplasia accounts for the severalfold increase in adipose tissue mass that occurs throughout life, yet the mechanism of adipocyte hyperplasia is unknown. We studied the potential of macrophage colony-stimulating factor (MCSF) to mediate adipocyte hyperplasia because of the profound effects MCSF exerts on pluripotent cell recruitment and differentiation in other tissues. We found that MCSF mRNA and protein were expressed by human adipocytes and that adipocyte MCSF expression was upregulated in rapidly growing adipose tissue that encircled acutely inflamed bowel and in adipose tissue from humans gaining weight (4-7 kg) with overfeeding. Localized overexpression of adipocyte MCSF was then induced in rabbit subcutaneous adipose tissue in vivo using adenoviral-mediated gene transfer. Successful overexpression of MCSF was associated with 16-fold increases in adipose tissue growth compared with a control adenovirus expressing beta-galactosidase. This occurred in the absence of increased cell size and in the presence of increased nuclear staining for MIB-1, a marker of proliferation. We conclude that MCSF participates in adipocyte hyperplasia and the physiological regulation of adipose tissue growth.

Adenoviridae↗
PubMed1998

Pituitary desensitization to gonadotropin-releasing hormone increases abdominal adiposity in hyperandrogenic anovulatory women.

OBJECTIVE: To determine whether hyperandrogenism in anovulatory women affects body fat distribution. DESIGN: Prospective nonrandomized study. SETTING: An academic research environment. PATIENT(S): Ten hyperandrogenic anovulatory patients and 10 healthy women matched by body mass index. INTERVENTION(S): Regional body fat analysis was performed before and after 3 months of GnRH analogue (GnRH-a) therapy. MAIN OUTCOME MEASURE(S): Body fat distribution was measured by waist-to-hip circumference ratio, single-slice computed tomography imaging (L2-3 interspace), and total body dual-energy x-ray absorptiometry. RESULT(S): Weight, body mass index, waist-to-hip circumference ratio, total body and leg fat mass, and subcutaneous adipose area were unaffected by the presence of hyperandrogenism or the use of GnRH-a therapy. Basal abdominal fat mass, abdomen-to-leg fat mass ratio, visceral adipose area, and total visceral adipose volume were comparable in both study groups. The abdominal fat mass increased in both groups during GnRH-a therapy, whereas the abdomen-to-leg fat mass ratio rose significantly only in the hyperandrogenic patients. During GnRH-a therapy, the hyperandrogenic patients demonstrated a significant increase in visceral adipose area compared with the healthy women so that total visceral adipose volume increased significantly in the former but not the latter. CONCLUSION(S): Three months of GnRH-a administration preferentially increased abdominal fat, as measured by single-slice computed tomography imaging and total body dual-energy x-ray absorptiometry, in hyperandrogenic anovulatory women.

Abdomen↗
PubMed1998

Effects of oral contraceptives on free fatty acid metabolism in women.

These studies examined whether women using oral contraceptives have abnormalities in free fatty acid (FFA) metabolism compared with women not using oral contraceptives. Plasma palmitate kinetics ([3H]palmitate) were measured at rest, following glucose ingestion, and during epinephrine infusion in 13 oral contraceptive users and 13 matched women not using oral contraceptives. Oral contraceptive users had significantly greater plasma triglyceride concentrations and glucose responses to oral glucose tolerance testing. No differences in basal (2.1 +/- 0.1 v 1.8 +/- 0.2 micromol x kg fat-free mass x FFM(-1) x min[-1]), glucose-suppressed (0.6 +/- 0.1 v 0.5 +/- 0.1 micromol x kg FFM(-1) x min[-1]), or epinephrine-stimulated (3.3 +/- 0.1 v 3.6 +/- 0.2 micromol x kg FFM(-1) x min[-1]) palmitate flux were detected between women using and not using oral contraceptives. The respiratory quotient (RQ) also was not different between groups. We conclude that the increase in plasma triglycerides and the mild glucose intolerance seen with oral contraceptive use is not associated with significant abnormalities of FFA metabolism.

Adult↗
PubMed1998

Diet effects on fatty acid metabolism in lean and obese humans.

The primary role of adipose tissue is to serve as a temporary storage site for energy in the form of nonesterified fatty acids. The regulation of adipose tissue lipolysis, which allows the appropriate delivery of fatty acids to meet the lipid fuel needs of lean tissue, is affected by the amount and the location of fat, as well as by the diet. Excessive accumulation of triacylglycerol fatty acids (obesity) is associated with an increased risk of insulin resistance, diabetes, hyperlipidemia, and hypertension. Some of these abnormalities may be related to dysregulation of fatty acid metabolism. Body fat distribution exerts a major influence on endogenous nonesterified fatty acid metabolism, which may in turn mediate some of the metabolic abnormalities associated with upper-body obesity. The effects of diet on fatty acid metabolism can be dramatic and are not the same in upper-body and lower-body obesity. Different obesity phenotypes may respond differently to low-fat, high-complex-carbohydrate diets, and the response is further modified depending on whether the diet is isoenergetic or restricted in energy.

Dietary Fats↗
PubMed1998

Effects of gender on resting leg blood flow: implications for measurement of regional substrate oxidation.

These studies were designed to examine whether the respiratory quotient (RQ) of leg tissue (primarily skeletal muscle) would increase to a greater degree in women than in men during meal ingestion. We found that mean leg and systemic RQ values were similar in men under both basal and fed conditions, whereas the agreement was poor in women. In women, leg RQ values tended to be greater than the systemic RQ, whereas splanchnic RQ values tended to be lower than the systemic RQ. The possibility that measurement imprecision accounted for the different findings in women could not be excluded because the arteriovenous blood O2 differences were almost twice as great in men as in women (53.7 +/- 5.4 vs. 28.6 +/- 2.9 ml of O2/l, respectively; P < 0.01), as were venoarterial blood CO2 differences. The smaller arteriovenous differences in women appeared to limit our ability to accurately measure their leg RQ values. O2 uptake relative to leg fat-free mass (FFM) was not different between men and women, whereas leg blood flow relative to leg FFM was greater in women than in men (55 +/- 3 vs. 39 +/- 2 ml.kg FFM-1.min-1, respectively; P < 0.001). These findings were confirmed by examining data from other studies conducted in our laboratory to create a larger data set. We conclude that resting leg blood flow in women is greater (relative to FFM) than in men, making it more difficult to accurately measure leg RQ in women.

Adult↗
PubMed1998

Intramuscular fatty acid metabolism evaluated with stable isotopic tracers.

We evaluated the applicability of stable isotopic tracers to the study of intramuscular fatty acid metabolism by infusing both [U-13C]palmitate and [1-13C]oleate intravenously for 4 h into fasted conscious rats. Skeletal muscles were sequentially biopsied, and the concentration and 13C enrichment of fatty acids were measured by gas chromatography/combustion/isotope ratio mass spectrometry. Throughout the study, the 13C enrichment of plasma palmitate and oleate remained substantially greater than intramuscular nonesterified palmitate and oleate enrichment, which in turn was greater than intramuscular triglyceride palmitate and oleate enrichment. Fractional synthesis rates of intramuscular triglycerides in gastrocnemius and soleus were 0.267 +/- 0.075 and 0. 100 +/- 0.030/h (P = 0.04), respectively, as determined by using [U-13C]palmitate, and were 0.278 +/- 0.049 and 0.075 +/- 0.013/h (P = 0.02), respectively, by using [1-13C]oleate. We conclude that plasma free fatty acids are a source for intramuscular triglycerides and nonesterified fatty acids; the latter are likely the synthetic precursors of the former. Uniformly and singly labeled [13C]fatty acid tracers will provide an important tool to study intramuscular fatty acid and triglyceride metabolism.

Animals↗
PubMed1998

Adenoviral-mediated gene transfer to human adipocytes in vitro, and human adipose tissue ex vivo and rabbit femoral adipose tissue in vivo.

Adenoviral-mediated gene transfer has proven useful in several organ systems to understand gene action and to provide a potential therapeutic modality for localized, organ-specific gene overexpression. However, the application of adenoviral-mediated gene transfer to adipocytes and adipose tissue has not been evaluated. We evaluated the feasibility of in vitro and ex vivo transfer of the beta-galactosidase gene to human adipocytes and adipose tissue by means of adenoviral vectors. The efficiency (percentage of cells transduced) of adenoviral-mediated gene transfer of the beta-galactosidase gene to human adipocytes in vitro and to human adipose tissue ex vivo was 21 +/- 3% and 14 +/- 3%, respectively. Adenoviral-mediated gene transfer in a rabbit femoral adipose tissue was also demonstrated in vivo. Adenoviral-mediated gene transfer may facilitate studies on understanding the biology of adipocytes and provide a potential tool for the modulation of adipocyte function in vivo and thereby for the treatment of obesity.

Adenoviridae↗
PubMed1998

Measurement of plasma glycerol specific activity by high performance liquid chromatography to determine glycerol flux.

Previous methods for measuring plasma glycerol specific activity (SA) are suboptimal, making the determination of glycerol kinetics in vivo with radiotracers difficult. A new high performance liquid chromatography (HPLC) method is described that permits the accurate and specific measurement of glycerol SA. The method involves isolation of glycerol from plasma and the formation of a tribenzoyl derivative. Glycerol rate of appearance was measured in five human volunteers using both [2-3H]glycerol and [2H5] glycerol. There was close agreement between the glycerol appearance rates measured using the two approaches (1.66 +/- 0.14 vs. 1.70 +/- 0.10 micromol x kg(-1) x min(-1), respectively, P = NS). This HPLC method offers improved specificity over existing methods of measuring glycerol turnover using radiotracers.

Chromatography, High Pressure Liquid↗
PubMed1998

Medical management of obesity.

Obesity is a heterogeneous condition. Some individuals suffer severe, life-threatening medical complications as a result of their obesity, whereas others appear to remain healthy for their entire lives despite substantially greater-than-normal amounts of body fat. A personal or family history of adverse health consequences of obesity and an upper-body fat distribution suggests that the patient will have greater health risks from obesity, and these patients stand to benefit more from successful treatment. Therefore, one can justify more aggressive approaches in helping them to make permanent changes in eating and exercise behavior, which are the cornerstones of obesity management. Supplementing these interventions with behavior therapy is necessary for patients unable to make lifestyle changes by themselves. Pharmacotherapy is appropriate for patients with medically complicated obesity in whom other approaches have not succeeded.

Behavior Therapy↗
PubMed1997

Obesity and cardiovascular disease: is body structure a factor?

Obesity is associated with increased cardiovascular morbidity and mortality. Individuals who predominantly store fat abdominally (particularly in the visceral area), more often present with an atherogenic lipid profile and are more frequently characterized by hemostatic, metabolic and anatomical abnormalities compatible with insulin resistance and increased atherothrombotic risk. Weight loss improves many of the cardiovascular risk factors associated with abdominal obesity.

Abdomen↗
PubMed1997

Lipolysis: contribution from regional fat.

In vitro studies of adipocytes taken from different body fat regions suggest substantial differences in lipolysis between intra-abdominal, lower-body subcutaneous, and abdominal subcutaneous regions. Gender and obesity appear to influence these regional differences. In situ measurements of glycerol release from adipose tissue provided further evidence that regional heterogeneity of lipolysis occurs in humans. In vivo studies of regional free fatty acid (FFA) release have confirmed that adipose tissue lipolysis varies between upper- and lower-body fat. Release of FFA from lower-body adipose tissue is less than that from upper-body adipose tissue in both obese and non-obese men and women. In non-obese men and women, meal ingestion suppresses FFA release from all adipose tissue regions, and adrenergic stimulation activated FFA release from different sites in a gender-specific fashion. Significant regional and gender differences in adipose tissue lipolysis occur in humans, and this could contribute to differences in the health effects of adipose tissue and could theoretically influence body fat distribution.

Abdomen↗
PubMed1997

Lipolytic responsiveness to epinephrine in nondiabetic and diabetic humans.

To determine whether the sensitivity of adipose tissue lipolysis to catecholamines is increased in poorly controlled insulin-dependent diabetes, the lipolytic response to epinephrine was measured in seven nondiabetic volunteers and seven poorly controlled diabetic subjects with use of [1-(14)C]palmitate as a tracer. Subjects received sequential 1-h infusions of epinephrine, which produced epinephrine concentrations of approximately 1,000, approximately 1,750, approximately 3,500, and approximately 6,000 pmol/l. A pancreatic clamp was used to maintain constant plasma hormone levels. Concentration-response curves were constructed for each subject from the integrated lipolytic response during each epinephrine infusion. There was no difference in maximal lipolytic response (117 +/- 19 vs. 152 +/- 11 mumol.kg-1.h-1) or in maximally effective (3,171 +/- 267 vs. 3,357 +/- 349 pmol/l) or half-maximally effective (1,081 +/- 109 vs. 1,015 +/- 120 pmol/l) epinephrine concentrations between nondiabetic and diabetic subjects, respectively (all P = NS). In control subjects, maximum beta-hydroxybutyrate concentrations were achieved at lower epinephrine concentrations than those required for a maximum lipolytic effect. Thus, under pancreatic clamp conditions, the lipolytic response to epinephrine in nondiabetic and diabetic subjects was similar.

3-Hydroxybutyric Acid↗
PubMed1997

Regional lipolytic responses to isoproterenol in women.

We previously found that epinephrine, a mixed beta- and alpha-adrenoreceptor agonist, stimulates systemic and nonsplanchnic upper body free fatty acid (FFA) release but not lower body FFA release in healthy nonobese women. To evaluate the role of beta-adrenergic-mediated effects on this regional difference in lipolysis, we measured systemic, leg, and splanchnic FFA kinetics ([3H]palmitate) in seven healthy nonobese women before and during an intravenous isoproterenol infusion. Isoproterenol increased systemic palmitate flux (87 +/- 12 vs. 100 +/- 10 mumol/min, P < 0.05) but failed to affect leg [10.8 +/- 1.2 vs. 11.4 +/- 2.3 mumol/min, P = not significant (NS)] or splanchnic (10.8 +/- 3.2 vs. 10.0 +/- 1.8 mumol/min, P = NS) palmitate release. Upper body nonsplanchnic palmitate release increased from 56 +/- 14 to 71 +/- 10 mumol/min. Systemic O2 consumption increased (227 +/- 11 to 241 +/- 10 ml/min, P = 0.006) during isoproterenol infusion, as did leg (318 +/- 42 vs. 404 +/- 53 ml/min, P < 0.01) and splanchnic (827 +/- 104 vs. 970 +/- 108 ml/min, P < 0.05) plasma flow. These results suggest that lower body adipose tissue lipolysis in women is less sensitive or responsive than nonsplanchnic upper body adipose tissue to beta-adrenergic stimulation and that regional differences in alpha 2-adrenergic-receptor responses were not responsible for the similar regional differences we observed previously with epinephrine.

Adult↗
PubMed1997

Localization of leptin receptor in the human brain.

Leptin (OB protein), the product of the adipose-specific ob gene, exerts important effects in the regulation of food intake and energy expenditure. Based upon results from animal studies, several groups have suggested that this action may be exerted in the brain, specifically in the hypothalamic region. However, to date, the localization of the OB-R in the human brain has not been described. One aim of this study was to contribute to a better understanding of the role that the central nervous system plays in the pathogenesis of obesity in humans. A first stage was to determine the OB-R expression in the human brain by means of immunohistochemistry and Western blotting. Several brain regions from 17 lean, 14 obese, and 4 diabetic (NIDDM) subjects, obtained from archival autopsy material, were sampled. Brain samples from neocortex, hypothalamus, medualla, limbic system, pineal and cerebellum were routinely processed in paraffin and analyzed with the avidin-biotin immunoperoxidase and diaminobenzidine detection method. Western blotting (WB) analysis was done on fresh brain tissue from an obese patient. Specific OB-R immunoreactivity was localized in the choroid plexus epithelium, ependymal lining, and neurons of the hypothalamic nuclei (arcuate, suprachiasmatic, mamillary, paraventricular, dorsomedial, supraoptic and posterior), nucleus basalis of Meynert, inferior olivary nuclei and cerebellar Purkinje cells. No differences in OB-R immunoreactivity were found among the three groups examined. WB analysis yielded 97- and 125-kD bands in the hypothalamus and cerebellum. In summary, this paper presents the first evidence to indicate the specific localization of the OB-R in the brain of lean, obese and NIDDM subjects.

Blotting, Western↗
PubMed1997

Health consequences of fat distribution.

Body fat distribution is now recognized as an important predictor of the adverse health consequences of obesity. Upper body obesity, especially with increasing visceral fat, is associated with hypertension, insulin resistance, dyslipidemia, type II diabetes mellitus and premature coronary death. Several lines of evidence suggest that abnormal adipose tissue lipolysis, resulting in elevated free fatty acid (FFA) availability, may contribute to some of the metabolic consequences of upper body obesity. The vast majority of the elevated systemic FFA release appears to come from upper body, non-splanchnic adipose tissue. Thus, dysregulation of upper body, non-splanchnic adipose tissue lipolysis may play an important role in contributing to health consequences of fat distribution.

Adipose Tissue↗