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Biomedical subjects

M D Jensen

Publications and source records attributed to M D Jensen.

At least 91 records · Page 5Linked to original sources

Differential health benefits of weight loss in upper-body and lower-body obese women.

Upper-body obesity (UB Ob) is more strongly associated with adverse health consequences; however, few obesity-treatment studies have examined outcome according to body-fat distribution. To examine whether diet and formal- or informal-exercise instruction causes differential changes in health and lipid profiles, ten LB Ob and nine UB Ob premenopausal women received dietary intervention (2.1 MJ-deficit/d for 16 wk) and were randomly assigned to either formal- or informal-exercise instruction. Weight loss was similar between groups (approximately 8 kg), and no change occurred in lean body mass or basal metabolic rate. Baseline cholesterol and triglycerides were greater (P < 0.01) in UB Ob than LB Ob women and decreased more (P < 0.01) in response to treatment in UB Ob women. Formal exercise instruction increased high-density-lipoprotein cholesterol (P < 0.05) especially in UB Ob women. Future studies on treatment of obesity should include consideration of regional fat distribution.

Adipose Tissue↗

Effects of exercise and weight loss on leucine turnover in different types of obesity.

These studies were performed to determine whether protein turnover during exercise and after weight loss is influenced by obesity and body fat distribution. Leucine carbon flux was measured before, during, and after 2.5 h of bicycle exercise in 10 upper body obese, 9 lower body obese, and 6 nonobese, age-matched, premenopausal women. The obese women then followed an energy-restricted diet for 16 wk, resulting in approximately 8 kg weight loss. Baseline leucine carbon flux was greater (P < 0.01) in obese women than in nonobese women but decreased in a similar fashion in response to exercise in all groups. There were no differences between upper body and lower body obese women during exercise. After weight loss, baseline leucine carbon flux decreased (P < 0.05) similarly in both groups of obese women and was further suppressed by exercise. Thus obesity phenotype has no specific effect on either baseline protein turnover or the antiproteolytic response to moderate intensity exercise or weight loss. We conclude that the previously observed defect in insulin suppression of leucine flux in upper body obese women appears related to insulin resistance and does not represent an inherent abnormality of protein metabolism.

Adult↗

Fatty acid kinetic responses to exercise. Effects of obesity, body fat distribution, and energy-restricted diet.

UNLABELLED: Upper body obesity (UB Ob) is associated with a reduced net free fatty acid (FFA) response to epinephrine compared with nonobese (Non Ob) and lower-body obese (LB Ob) women. Because catecholamines regulate some of the metabolic responses to exercise, we hypothesized that UB Ob would have a reduced net FFA response to exercise. Plasma FFA rate of appearance (Ra) ([1-14C]palmitate) and fatty acid oxidation (indirect calorimetry) were therefore measured during 2.5 h of stationary bicycle exercise (45% VO2 peak) in 13 UB Ob, 11 LB Ob, and 8 Non Ob premenopausal women. 10 UB Ob and 8 LB Ob women were retested after an approximately 8-kg weight loss. RESULTS: During exercise Non Ob and LB Ob women had greater increments in FFA availability (51 +/- 7 and 53 +/- 8 mmol, respectively) than UB Ob women (27 +/- 4 mmol, P < 0.05). Total exercise FFA availability and fatty acid oxidation were not different between Non Ob, LB Ob, and UB Ob women, however. Following weight loss (approximately 8 kg), the FFA response to exercise increased (P < 0.01) and remained greater (P < 0.05) in LB Ob than in UB Ob women. In conclusion, the FFA response to exercise was reduced in UB Ob women before and after weight loss, but no effects on fatty acid oxidation were apparent.

Body Composition↗

Body-composition changes in patients who gain weight while receiving megestrol acetate.

PURPOSE: Randomized placebo-controlled clinical trials have now established that megestrol acetate causes appetite stimulation and weight gain in patients with anorexia and/or cachexia. There is a paucity of available data to delineate the substance of this increased weight. PATIENTS AND METHODS: Using dual-energy x-ray absorptiometry and tritiated body water methodologies, we performed body-composition measurements in 12 patients with advanced cancer before the institution of oral megestrol acetate (800 mg/d) and at subsequent 2-month intervals. RESULTS: Seven of the 12 patients gained weight (2.1 to 16.5 kg) and had repeat body-composition measurements performed at the time of maximum weight gain. The vast majority of the gained weight was clearly from an increase in adipose tissue, while there was a suggestion that an increase in body fluid was responsible for a minority of the weight gain. CONCLUSION: Megestrol acetate-induced weight gain is primarily the result of an increase in body mass.

Anorexia↗

Postprandial free fatty acid kinetics are abnormal in upper body obesity.

Excess free fatty acid release (rate of appearance) is seen in overnight postabsorptive, upper body obese women and, if present postprandially, could contribute to glucose intolerance. These studies examine the antilipolytic effect of a mixed meal in upper body obese, lower body obese, and nonobese women and the contribution of meal triglyceride fatty acids to circulating free fatty acids. Eight upper body obese, 8 lower body obese, and 8 nonobese age-matched, premenopausal women were studied. Systemic oleate Ra ([3H]oleate) was measured before and after an evening meal that contained triolein labeled with [14C]triolein as the only source of fat. Premeal oleate Ra was greater in both upper body obese and lower body obese women than nonobese women. The nadir of total oleate Ra occurred 90-240 min postprandially and was less (P < 0.01) in nonobese and lower body obese women (63 +/- 10 and 87 +/- 17 mumol/min) than in upper body obese women (140 +/- 21 mumol/min). Meal oleate Ra contributed substantially to total oleate Ra. The nadir for endogenous oleate Ra in nonobese and lower body obese women was less (P < 0.01) than that observed in upper body obese women. We conclude that the antilipolytic effect of a mixed meal is reduced in upper body obese women and that meal triglyceride fatty acids contribute significantly to postprandial free fatty acid flux.

Adult↗

Effect of megestrol acetate on the human pituitary-adrenal axis.

A few previous reports have suggested that megestrol acetate, a synthetic progestational agent frequently used as an antineoplastic drug, suppresses serum cortisol concentrations in humans. To explore this concept further, we prospectively performed several measurements of the pituitary-adrenal axis in patients receiving megestrol acetate (160 or 800 mg/day). The data from these evaluations demonstrate that megestrol acetate reversibly decreases serum cortisol concentrations in humans and that this effect seems to originate from a suppression of the pituitary-adrenal axis. Additional studies should be conducted to determine the implications of the low levels of serum cortisol.

Humans↗

Free fatty acid metabolism in the follicular and luteal phases of the menstrual cycle.

To determine whether the hormonal changes associated with the normal menstrual cycle influence FFA metabolism, FFA turnover was measured in 12 women during both the follicular (days 4-10) and luteal (days 18-24) phases of their menstrual cycles. The luteal phase was confirmed by increased serum progesterone concentrations. Overnight postabsorptive FFA flux was similar in the follicular and luteal phases of the menstrual cycle (6.9 +/- 0.8 vs. 5.8 +/- 0.5 mumol kg-1 min-1, respectively, P = NS). In addition, the FFA response to 3 h of somatostatin-induced hypoinsulinemia was virtually identical on both study days. Finally, we compared the intraindividual variability of basal FFA flux from studies performed in different vs. the same phase of the menstrual cycle; no difference was present. We conclude that the cyclic changes in estrogen and progesterone production which occur during the normal menstrual cycle appear to have minor, if any, effects on FFA mobilization.

Adult↗

Insulin regulation of insulin-like growth factor binding protein-1 in obese and nonobese humans.

Insulin is the principal regulator of hepatic insulin-like growth factor binding protein-1 (IGFBP-1) production, mediating the rapid decrease in plasma IGFBP-1 in response to nutritional intake. In this study, we defined IGFBP-1 regulation by insulin in upper and lower body obesity, conditions associated with insulin resistance and chronic hyperinsulinemia. Overnight postabsorptive IGFBP-1 levels in obese and nonobese women showed an inverse, nonlinear relationship with plasma insulin concentrations. Maximum suppression of IGFBP-1 was seen at 70-90 pmol/L plasma insulin. Both groups of obese women had mean fasting plasma insulin concentrations above this threshold level and, consequently, markedly suppressed IGFBP-1 levels. To assess the dynamics of insulin regulated IGFBP-1, 10 obese and 8 nonobese women were studied during sequential saline infusion (0-90 min), hyperinsulinemia (insulin infusion; 90-210 min) and hypoinsulinemia (somatostatin + GH infusion; 210-330 min). Insulin infusion rapidly decreased plasma IGFBP-1 levels in nonobese subjects (60% decrease in 2 h), but had little or no further suppressive effect in obese subjects. Complete insulin withdrawal resulted in a significant rise in plasma IGFBP-1 concentrations in all subjects, but the response was blunted in obese compared to nonobese groups. In contrast to plasma IGFBP-1, IGF-I concentrations did not vary during hyper- and hypoinsulinemic infusion periods and were not significantly different between groups. Basal GH levels were significantly higher in nonobese when compared to obese women, but did not change with infusions. In conclusion, low IGFBP-1 levels in obesity are related to elevated insulin levels which are, in turn, related to body fat distribution and insulin resistance. The chronically depressed levels of IGFBP-1 may promote IGF bioactivity as well as its feedback regulation of GH secretion, thus contributing to the metabolic and mitogenic consequences of obesity. In addition, our findings imply that hepatic insulin sensitivity in terms of IGFBP-1 production is preserved despite peripheral insulin resistance in obesity.

Adult↗

Research techniques for body composition assessment.

Although a variety of techniques are currently available to measure body composition in human beings, each has limitations with respect to its applicability in addressing nutrition research issues. Several methods "directly" determine an individual's body fat or lean tissue mass with sufficient precision and accuracy such that the data are appropriate for making fine distinctions between individuals or within an individual over time. Such direct methods are most useful in nutritional/metabolic research that requires such distinctions. Each of these techniques will be discussed. There also exist a number of "indirect" measures of body composition. These techniques require more interpretative assumptions and are perhaps better suited to population studies, in which it is often less critical to make fine distinctions between individuals. The appropriate design and interpretation of many nutrition-related research studies depend upon the correct use of body composition data. This review will attempt to help the reader understand the principles of each of the currently available body composition techniques and its optimal use.

Absorptiometry, Photon↗

Heated hand vein blood is satisfactory for measurements during free fatty acid kinetic studies.

Quantitatively accurate measurements of plasma free fatty acid (FFA) turnover can be made if the FFA tracer is infused intravenously and arterial blood is sampled. To be certain that arterialized-venous blood provides comparable information, plasma FFA concentration and specific activity were measured in both arterial and arterialized-venous blood in 19 volunteers undergoing infusion of [1-14C]palmitate infusion before and during a euglycemic, hyperinsulinemic clamp. Heated hand vein blood was obtained using either the heated box (n = 9 subjects) or heating pad (n = 10 subjects) technique. The heated box arterialized-venous blood had palmitate concentration and specific activity equal to arterial blood. The use of the heating pad resulted in small (3%), but statistically significant (P less than .05), underestimates of palmitate specific activity. In addition, plasma lactate concentrations were significantly higher in heated hand vein blood than arterial blood. In summary, heated hand vein blood is a satisfactory alternative to arterial blood for tracer studies of FFA metabolism.

Adult↗

Effects of intravenous methyl palmoxirate on the turnover and oxidation of fatty acids in conscious dogs.

Methyl palmoxirate (MP) is a member of a class of hypoglycemic agents that inhibit fatty acid oxidation in vitro. The studies presented here were undertaken to determine the effects of intravenous (IV) MP on tracer-determined rates of fatty acid oxidation and systemic adipose tissue lipolysis in dogs. MP (40 mg/kg) was administered IV to five mongrel dogs using a primed continuous infusion of [1-14C]palmitate to determine palmitate kinetics. Palmitate concentration and rate of appearance decreased rapidly (from 155 +/- 25 to 47 +/- 6 mumol/L and 2.9 +/- 0.5 to 0.9 +/- 0.2 mumol.kg-1.min-1, respectively, at 15 minutes, both P less than .05). Palmitate oxidation also decreased, from 1.5 +/- 0.4 to 0.3 +/- 0.1 mumol.kg-1.min-1, P less than .05. Oxidative clearance decreased by approximately 50% 90 minutes after MP administration (P less than .05). Fractional oxidation of palmitate also decreased by approximately 40% (P less than .05). Plasma insulin increased from 45 +/- 6 to 240 +/- 93 pmol/L at 15 minutes (P less than .05). Plasma glucose decreased over the course of study by approximately 20% (P less than .05). In summary, MP has a specific inhibitory effect on plasma free fatty acid (FFA) oxidation in dogs, confirming previous in vitro observations in an in vivo model. In addition, it has a potent antilipolytic effect when administered IV, an effect likely mediated by stimulation of insulin secretion. The observation that systemic FFA oxidation was only partially suppressed at this relatively high dose of MP is consistent with previous studies suggesting that MP may exert its major effect in the liver, and may be less potent in extrahepatic tissues.

Animals↗

Prospective evaluation of vertical banded gastroplasty as the primary operation for morbid obesity.

Our previous experience with vertical (nonbanded) gastroplasty proved disappointing because of unsatisfactory maintenance of weight loss. Vertical banded gastroplasty seemed to be an attractive alternative operation because it provided an externally reinforced (banded) stoma that would not enlarge over time. In this study, our aim was to determine prospectively the results of vertical banded gastroplasty used as a primary, weight-reducing procedure in patients with morbid obesity. Seventy consecutive patients with morbid obesity (mean weight, 139 kg), all of whom had obesity-related complications, underwent vertical banded gastroplasty and prospective follow-up. The hospital mortality was nil, and substantial morbidity occurred in 3% (two patients). Long-term achievement and maintenance of satisfactory weight loss, however, were variable. The median weight loss at 1 year after operation was 36.7 kg or 48% of excess body weight. At 3 years postoperatively, however, weight loss was only 32.4 kg or 40% of excess body weight, and only 38% of patients had achieved and maintained a weight loss of 50% or more of their preoperative excess body weight. Vertical banded gastroplasty caused major changes in eating habits, and many patients were unable to eat red meat or untoasted bread; moreover, approximately 30 to 50% of patients continued to vomit once or more per week. Despite theoretically attractive advantages as a weight-reduction operation, vertical banded gastroplasty does not seem to be the optimal procedure for most patients with morbid obesity.

Adult↗

Adrenergic regulation of lipolysis in a patient with lipoatrophy of the upper body.

A patient with lipoatrophy of the upper body had laboratory evidence of increased activity of the adrenergic nervous system. Because the adrenergic nervous system is important in the regulation of lipolysis, studies were performed to determine whether lipolysis of the upper body was ongoing in this patient and whether pharmacologic reduction of activity of the adrenergic nervous system would affect lipolysis of adipose tissue. Release of free fatty acids from systemic and forearm adipose tissue was measured before and after the administration of guanfacine hydrochloride. Forearm adipose tissue, although decreased in quantity, was found to release normal amounts of free fatty acids. Systemic and forearm release of free fatty acids decreased after 3 days of treatment with guanfacine. These results suggest that lipoatrophy of the upper body in some patients may be mediated through dysfunction of the adrenergic nervous system. These findings also emphasize the potential for heterogeneous responses of adipose tissue to hormonal regulatory factors.

Adipose Tissue↗

Protein metabolism in obesity: effects of body fat distribution and hyperinsulinemia on leucine turnover.

To examine whether moderate obesity and differences in body fat distribution are associated with abnormalities of protein metabolism, leucine turnover was measured in three groups of age-matched premenopausal women. Ten upper-body-obese (UB Ob), 10 lower-body-obese (LB Ob), and 10 nonobese (Non Ob) women were studied in an overnight postabsorptive condition (basal) and again during an infusion of low physiologic amounts of insulin (insulin clamp). Results showed that basal leucine carbon flux was greater (P less than 0.05) in UB Ob and LB Ob women than in Non Ob women (2.96 +/- 0.08 vs 3.14 +/- 0.16 vs 2.68 +/- 0.08 mumol.kg lean body mass-1.min-1, respectively; mean +/- SEM). Leucine carbon flux was not suppressed during the insulin-clamp study in UB Ob women but was in the LB Ob and Non Ob women. We conclude that moderate obesity is associated with increased proteolysis and that insulin's antiproteolytic actions are impaired in upper-body obesity. These findings could have implications for future studies of and treatment of obesity.

Adipose Tissue↗

How valid are isotopic measurements of fatty acid oxidation?

These studies were performed 1) to compare two isotopic methods (3H2O and 14CO2 production) of measuring free fatty acid (FFA) oxidation; 2) to determine whether isotopic estimates of fatty acid oxidation during hypoinsulinemia are plausible when compared with those obtained using indirect calorimetry; and 3) to examine whether the delay between the exit of [14C]FFA from plasma and the appearance of 14CO2 in breath is accounted for solely by bicarbonate kinetics. Studies in 11 healthy volunteers revealed that [14C]- and [3H]FFA tracers provide similar estimates of FFA turnover and oxidation. Isotopic estimates of fatty acid oxidation were less than those of indirect calorimetry under basal conditions but equaled or exceeded indirect calorimetry estimates after 3 h of acute hypoinsulinemia (somatostatin induced). After stopping tracer infusions, the half-life of plasma [14C]FFA was 3.7 +/- 0.1 min. The half-life of 14CO2 decay from [14C]bicarbonate was 37 +/- 1 min, and the half-life of 14CO2 decay after discontinuation of [14C]FFA infusion was 141 +/- 10 min. Intracellular preoxidative fatty acid pools (possibly triglycerides) most probably account for the marked delay between the exit of FFA tracers from plasma and the appearance of isotopic markers of oxidation in measurable spaces. This delay can result in erroneous estimates of "FFA oxidation." We conclude that tracer measurements of FFA oxidation are invalid under most circumstances.

Adult↗

Regulation of forearm lipolysis in different types of obesity. In vivo evidence for adipocyte heterogeneity.

UNLABELLED: Forearm and systemic adipose tissue free fatty acid (FFA) release was measured in eight nonobese, six lower-body obese, and eight upper-body obese women under basal, hyperinsulinemic, and hypoinsulinemic conditions to determine whether forearm fat is regulated in a similar manner as whole body fat. RESULTS: Adipose tissue palmitate release was greater from forearm than whole body (5.97 +/- 0.75 vs. 3.84 +/- 0.34 mumol.kg fat-1.min-1, respectively, P less than 0.005, n = 22 subjects). Systemic palmitate release, relative to fat mass, was significantly (P less than 0.01) greater in nonobese than upper-body obese, and upper-body obese than lower-body obese women, and forearm adipose tissue palmitate release followed the same pattern. Hyperinsulinemia suppressed systemic and forearm lipolysis to similar degrees, however, hypoinsulinemia consistently increased systemic palmitate flux without increasing forearm palmitate release. These results confirm the heterogeneity of adipose tissue in an in vivo model and emphasize the need to consider which adipose tissue depots are responsible for the differences in systemic FFA flux in obese and nonobese humans.

Adipose Tissue↗

Effects of body fat distribution on regional lipolysis in obesity.

UNLABELLED: To determine the contribution of the major body fat depots to systemic free fatty acid (FFA) availability, palmitate ([1-14C]-palmitate) release was measured from leg (lower body) and non-leg (upper body) fat in eight upper body obese (UB Ob), six lower body obese (LB Ob), and six nonobese (Non Ob) age-matched premenopausal women in the overnight postabsorptive state. Splanchnic palmitate release was determined in 16 of these subjects. RESULTS: total palmitate release was greater in UB Ob (P less than 0.005) than LB Ob or Non Ob women (161 +/- 16 vs. 111 +/- 9 vs. 92 +/- 9 mumol/min, respectively). Despite increased leg fat mass in obese women, leg palmitate release was similar in each group. Therefore, leg fat palmitate release was greater in Non Ob women than LB Ob (P less than 0.01) or UB Ob (P = 0.06) women (3.7 +/- 0.3 vs. 2.4 +/- 0.2 vs. 2.7 +/- 0.2 mumol.kg fat-1.min-1, respectively). Upper body fat palmitate release was less (P less than 0.01) in LB Ob than Non Ob or UB Ob women (3.0 +/- 0.4 vs. 5.0 +/- 0.3 vs. 4.9 +/- 0.4 mumol.kg fat-1.min-1, respectively). Splanchnic palmitate release accounted for 20-32% of upper body fat palmitate release in each group (P = NS between groups). Leg fat palmitate release was significantly less than upper body fat palmitate release. We conclude that the major difference in resting FFA metabolism between UB Ob and LB Ob women is the ability of the later to down-regulate upper body fat lipolysis to maintain normal FFA availability.

Adipose Tissue↗