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M D Jensen

Publications and source records attributed to M D Jensen.

At least 73 records · Page 4Linked to original sources

Free fatty acid turnover measured using ultralow doses of [U-13C]palmitate.

Low intravenous infusion rates of [U-13C]palmitate were used to measure systemic palmitate flux at rest (0.5 nmol . kg-1 . min-1) and during exercise (2 nmol . kg-1 . min-1) in healthy adults. The 13C enrichment of plasma palmitate was determined by gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). Palmitate flux was also measured using palmitate radiotracers, which were infused simultaneously to serve as a reference method. Flux values obtained using the two different methods were virtually identical. Overnight postabsorptive palmitate flux was measured on four occasions in three individuals; the flux values were highly reproducible with a coefficient of variation of 11% and 12% for intra-day measurement, and 13% and 8% for inter-day measurement, for [1-(14)C]palmitate and [U-(13)C]palmitate, respectively. During exercise, palmitate turnover measured with [U-(13)C]palmitate and [3H]palmitate were well correlated (r = 0.91). Compared to conventional stable isotope approaches, (e.g., [1-(13)C]palmitate analyzed by GC/MS), [U-(13)C]palmitate reduces the tracer dose by two orders of magnitude when the samples are analyzed with GC/C/IRMS. Uniformly labeled [13C]palmitate is suitable for the measurement of free fatty acid flux in humans.

Adult↗

Contribution of leg and splanchnic free fatty acid (FFA) kinetics to postabsorptive FFA flux in men and women.

We have previously shown that upper-body adipose tissue is more lipolytically active than lower-body adipose tissue in lean and obese women. The present studies were conducted to determine whether these regional differences are also present in men. Twenty-five lean, healthy men and 24 lean, healthy women underwent measures of body composition, postabsorptive systemic free fatty acid (FFA) flux, and leg and splanchnic FFA uptake and release. Upper-body adipose tissue was more lipolytically active than lower-body adipose tissue in both men (53.4 +/- 32.2 v 26.6 +/- 12.9 micromol x kg fat(-1) x min(-1), P < .001, respectively) and women (41.2 +/- 22.3 v 18.4 +/- 8.2 micromol x kg fat(-1) x min(-1), P < .001, respectively). The correlations between leg FFA release and systemic FFA flux were modest in women and men (r = .38, P = .07 and r = .56, P = .003, respectively) as were the correlations between splanchnic FFA release and systemic FFA flux (r = .41, P = .06 and r = .40, P = .07, respectively). No effect of gender on the relationship between leg or splanchnic FFA release and systemic FFA flux was detected. In summary, upper-body FFA release is greater than lower-body FFA release in both men and women, and the relationship between leg or splanchnic FFA release and systemic FFA release is weak and similar in men and women. These findings suggest that regional differences in postabsorptive FFA kinetics are unlikely to be responsible for differences in regional fat distribution.

Absorption↗

Effects of epinephrine on regional free fatty acid and energy metabolism in men and women.

Upper-body and lower-body adipocytes respond differently to physiological catecholamines in vitro. It is not known whether this is true in vivo or whether gender differences exist in the regional adipose tissue responses to epinephrine. These studies were therefore conducted to examine free fatty acid (FFA) release ([3H]palmitate) from lower-body (leg), splanchnic, and upper-body adipose tissue in normal-weight adult men (n = 8) and women (n = 7). In response to intravenous epinephrine (10 ng.kg-1.min-1), palmitate release increased (P < 0.01) in both men (168 +/- 10 to 221 +/- 15 mumol/min) and women (177 +/- 12 to 234 +/- 18 mumol/min). Basal leg palmitate release was similar in women and men (16.8 +/- 2.9 and 12.4 +/- 1.3 mumol/min, P = not significant) but doubled (P < 0.01) in response to epinephrine in men and was virtually unchanged in women. Splanchnic palmitate release increased (P < 0.05) in men (n = 6) but not in women (n = 6), whereas nonsplanchnic upper-body palmitate release increased more in women than in men. Upper-body (splanchnic and nonsplanchnic) palmitate release increased (P < 0.05) in both men and women in response to epinephrine. In summary, lower-body adipose tissue FFA release increased in response to epinephrine in men but not women, whereas upper-body palmitate release increased in both groups. These findings are consistent with some in vitro findings and suggest that catecholamine action may play a role in determining gender-based differences in body fat distribution.

Adult↗

Postprandial leg and splanchnic fatty acid metabolism in nonobese men and women.

These studies were conducted to determine whether there are gender-specific regional differences in meal triglyceride fatty acid uptake. Systemic and regional oleate ([3H]oleate) kinetics were measured in nine nonobese men and eight nonobese women before and at the end of a 6-h meal, administered as small frequent feedings to achieve steady-state chylomicronemia. Chylomicron uptake in the splanchnic bed accounted for 71 +/- 15% of meal triglyceride disappearance in men and 20 +/- 7% in women (P < 0.01), whereas leg chylomicron uptake could only account for 12 +/- 2 and 8 +/- 4% (P not significant in men vs. women) of meal triglyceride disappearance. Meal ingestion suppressed (P < 0.05) systemic and regional free fatty acid release in both men and women. Splanchnic nonchylomicron triglyceride release and leg nonchylomicron triglyceride uptake were not significantly different in men and women. In summary, the largest quantitative difference between men and women in fatty acid kinetics during meal ingestion is a substantially greater splanchnic uptake of meal triglyceride fatty acids in men. This could represent greater meal fatty acid storage in visceral adipose tissue.

Adult↗

Technical and practical considerations involved in operations on patients weighing more than 270 kg.

Care of the patient with superobesity requires special precautions and appropriate equipment. Recently, we performed bariatric procedures (modified very-long-limb Rouxen-Y gastric bypass) on patients weighing 355 kg and 377 kg. These procedures required preoperative preparation concerning safe means of transport of the patient, techniques of anesthesia and intraoperative exposure, provisions for postoperative recovery, and measures to assure patient comfort and hygiene postoperatively. In addition to specially designed bariatric procedures for the superobese, specialized equipment is needed to protect the health of the patient and the staff. All health care providers and especially acute care centers must have preconceived protocols to treat the superobese patient. In addition, specialized equipment is necessary to allow safe transport and support of these patients.

Adult↗

Measurement of abdominal and visceral fat with computed tomography and dual-energy x-ray absorptiometry.

These studies were undertaken to compare dual-energy x-ray absorptiometry (DXA) and computed tomography (CT) measurements of abdominal fat and to determine whether anthropometry could be combined with DXA to predict intraabdominal (visceral) fat mass in humans. Twenty-one volunteers underwent abdominal CT scans, DXA, and anthropometry. DXA- and CT-measured total abdominal fat were similar (8448 +/- 5005 and 8066 +/- 5354 mL, respectively; NS) and were highly correlated (r = 0.985, P < 0.001). The combination of anthropometry and DXA was a suboptimal predictor of CT-measured intraabdominal fat (r = 0.61, P < 0.05); however, the combination of a single CT slice (to assess the ratio of intraabdominal to total abdominal adipose tissue) and DXA-measured abdominal fat was an excellent predictor of CT-measured intraabdominal fat (r = 0.98, P < 0.001). We conclude that a single-slice CT scan (or other imaging technique) with or without DXA is required for accurate predictions of intraabdominal fat.

Absorptiometry, Photon↗

Thermogenesis after a mixed meal: role of leg and splanchnic tissues in men and women.

To determine the relative contribution of splanchnic and leg tissues to postprandial thermogenesis, systemic and regional oxygen consumption rates were measured in nine women and eight men before and for 6 h after the consumption of a mixed meal that provided one-third of the daily energy needs. In women, the increase in splanchnic oxygen uptake accounted for 63 +/- 12% of the postprandial increase in oxygen consumption, whereas in men it accounted for 35 +/- 14% (P = not significant between women and men). Leg oxygen uptake accounted for 11 +/- 4 and 10 +/- 3% of the increase in postprandial oxygen consumption in women and men, respectively. The combined data suggest that approximately 48% of postprandial thermogenesis over 6 h occurs in splanchnic tissues, whereas 30-35% occurs in skeletal muscle. Thus the increase in oxygen consumption after a mixed meal is primarily localized to splanchnic tissues, and major reductions in postprandial thermogenesis are unlikely to be attributable solely to abnormalities of skeletal muscle metabolism.

Adult↗

Fatty acid kinetic responses to running above or below lactate threshold.

During running exercise above the lactate threshold (LT), it is unknown whether free fatty acid (FFA) mobilization can meet the energy demands for fatty acid oxidation. This study was performed to determine whether FFA availability is reduced during running exercise above compared with below the LT and to assess whether the level of endurance training influences FFA mobilization. Twelve marathon runners and 12 moderately trained runners ran at a workload that was either above or below their individual LT. Fatty acid oxidation (indirect calorimetry) and FFA release ([1-14C]palmitate) were measured at baseline, throughout exercise, and at recovery. The plasma FFA rate of appearance increased during exercise in both groups; running above or below the LT, but the total FFA availability for 30 min of exercise was greater (P < 0.01) in the below LT group (marathon, 23 +/- 2 mmol; moderate, 21 +/- 2 mmol) than in the above LT group (18 +/- 3 and 13 +/- 3 mmol, respectively). Total fatty acid oxidation (indirect calorimetry) greatly exceeded circulating FFA availability, regardless of training or exercise group (P < 0.01). No statistically significant exercise intensity or training differences in fatty acid oxidation were found (above LT: marathon, 71 +/- 12, moderate, 64 +/- 17 mmol/30 min; below LT: marathon 91 +/- 12, moderate, 60 +/- 5 mmol/30 min). In conclusion, during exercise above or below LT, circulating FFA cannot meet the oxidative needs and intramuscular triglyceride stores must be utilized. Further marathon training does not enhance effective adipose tissue lipolysis during exercise compared with moderate endurance training.

Adipose Tissue↗

Gender differences in regional fatty acid metabolism before and after meal ingestion.

UNLABELLED: These studies were conducted to determine whether men and women differ with regards to their overnight postabsorptive (basal) and postprandial fatty acid kinetics. Systemic oleate turnover ([9,10(3)H]oleate) was measured before and after the consumption of a mixed meal. Leg and splanchnic free fatty acid (FFA) uptake and release were measured, allowing the calculation of upper-body subcutaneous FFA release. RESULTS: basal oleate flux was virtually identical in men and women (3.0 +/- 3 versus 2.9 +/- 0.4 mumol.kg FFM-1.min-1), however, oleate Ra suppressed more in women than in men following meal ingestion (0.5 +/- 0.1 versus 0.8 +/- 0.1 mumol.kg FFM-1.min-1, P < 0.05). The fractional contribution of basal, regional FFA release to total FFA flux was not significantly different between men and women. In contrast, oleate release by upper-body subcutaneous adipose tissue was significantly greater (30 +/- 5 vs 8 +/- 3 mumol/min, respectively, P < 0.01) in men than in women during the meal nadir of FFA flux, whereas splanchnic oleate release was a greater percentage (39 +/- 7% vs 20 +/- 3%, respectively, P < 0.05) of nadir oleate Ra in women than in men. Thus, normal weight men and women differ significantly in the postprandial regulation of adipose tissue lipolysis in that men's upper-body subcutaneous adipose tissue is more resistant to the antilipolytic effects of meal ingestion. Differential regulation of regional adipose tissue lipolysis could contribute to the gender based differences in body fat distribution.

Adipose Tissue↗

Contribution of blood flow to leg glucose uptake during a mixed meal.

Insulin has important effects to increase skeletal muscle (leg) blood flow under euglycemic hyperinsulinemic clamp conditions and after oral glucose tolerance testing. The present studies examined the effects of mixed meal consumption on the components of leg glucose uptake (LGU) in lean, healthy adults. Seventeen men and women underwent measures of leg plasma flow and arteriovenous (AV) glucose difference before and for 6 h after a mixed meal providing one-third of daily energy expenditure. Another eight men and women underwent the same studies before and during the consumption of the same-size meal administered in small frequent feedings over 6 h. After the bolus meal, peak leg AV glucose gradient increased approximately fivefold (P < 0.001), whereas the peak increase in leg plasma flow was 20% (NS). No significant contribution of increased leg blood flow to the increase in postprandial LGU was apparent. Over the last 100 min of the frequent-feedings meal, the leg AV difference increased approximately fourfold (P < 0.001 vs. basal), whereas leg blood flow increased only by 16% (NS vs. basal). We conclude that after a mixed meal, leg (primarily skeletal muscle) blood flow does not increase enough for blood flow to be a major contributor to glucose uptake. These findings raise questions regarding the relative importance of insulin's hemodynamic effects in modulating glucose tolerance under more usual conditions.

Adult↗

Serum lipid responses to a eucaloric high-complex carbohydrate diet in different obesity phenotypes.

OBJECTIVE: To determine whether the eucaloric substitution of complex carbohydrates for dietary fat (15% of daily energy intake) affects plasma lipid concentrations differently in upper-body obese, lower-body obese, and nonobese women. DESIGN: We studied 23 premenopausal women before and after dietary intervention. MATERIAL AND METHODS: After the 23 subjects achieved weight maintenance on their usual high-fat diet (43% fat, 37% carbohydrates, and 20% protein), the 7 upper-body obese, 8 lower-body obese, and 8 nonobese women consumed a eucaloric, high-complex carbohydrate, low-fat diet (27% fat, 53% carbohydrates, and 20% protein) for 4 weeks in the Clinical Research Center. Before and after the high-carbohydrate diet, body composition and plasma lipids and apoproteins were measured. RESULTS: After the high-carbohydrate diet, fasting plasma triglyceride concentrations increased (from 1.50 +/- 0.14 mmol/L to 2.00 +/- 0.25 mmol/L; P = 0.04) in upper-body obese women but were not significantly changed in lower-body obese (1.37 +/- 0.28 mmol/L and 0.96 +/- 0.12 mmol/L) or nonobese (0.70 +/- 0.08 mmol/L and 0.73 +/- 0.08 mmol/L) women. The hypertriglyceridemia was present before the evening meal and throughout the night in upper-body obese women. Plasma cholesterol and high-density lipoprotein cholesterol were not significantly affected by the change in diet. No changes in plasma apoprotein concentrations or body composition occurred that could account for the dietary-induced hypertriglyceridemia in the women with upper-body obesity. CONCLUSION: The hypertriglyceridemic response to a high-complex carbohydrate, low-fat diet may be obesity phenotype specific. These findings suggest that further studies of this phenomenon should be focused on this obesity phenotype and further emphasize the importance of assessing body fat distribution when treatment outcomes are determined.

Adult↗

Effects of isoenergetic, low-fat diets on energy metabolism in lean and obese women.

Whether changing from a high-fat diet to an isoenergetic, low-fat, high-complex-carbohydrate diet results in thermogenic benefits is controversial. Brief dietary interventions and failure to account for the potential influence of body-fat distribution on energy metabolism could have confounded the interpretation of previous studies. To address these issues, eight upper-body obese, seven lower-body obese, and eight non-obese premenopausal women underwent measurements of body composition, resting energy expenditure, overnight energy expenditure, and meal fat oxidation at the end of a weight-stabilizing, high-fat (42%) diet, and after 4 wk of an isoenergetic, low-fat (27%) diet. No change in body composition, resting energy expenditure, overnight energy expenditure, or meal fat oxidation occurred. We conclude that isoenergetic shifts from dietary fat to dietary carbohydrate within the generally recommended range have little or no effect on energy metabolism, and that body-fat distribution does not predict differences in energy expenditure.

Adipose Tissue↗

Effects of estrogen on free fatty acid metabolism in humans.

To determine whether estrogen directly affects effective adipose lipolysis, palmitate rate of appearances ([14C]palmitate) was measured in 15 postmenopausal women. Each volunteer was studied after > or = 2 mo of estrogen treatment and again after > or = 2 mo of estrogen deficiency. Plasma hormone concentrations were controlled and identical on the 2 study days with use of the pancreatic clamp technique, and the lipolytic response to epinephrine and epinephrine + phentolamine was assessed. Results showed that overall palmitate flux was greater (10-20%, P < 0.05) during the estrogen-deficient than during the estrogen-replete study. Adrenergic stimulation of lipolysis was not specifically influenced by estrogen treatment, and control of plasma hormone concentrations did not eliminate the difference in palmitate flux between the estrogen-deficient and estrogen-replete study days. We conclude that estrogen deficiency is associated with increased plasma free fatty acid availability and that estrogen likely has direct, albeit small, effects on adipose tissue lipolysis.

Blood Glucose↗

In vivo regulation of lipolysis in humans.

Fatty acids are important oxidative fuel for liver, kidney, skeletal muscle, and myocardium. There has been much interest in the role of fatty acids in the pathogenesis of non-insulin-dependent diabetes because they compete with glucose for oxygen and inhibit whole body glucose disposal via the 'Randle cycle,' Control of lipolysis in adipose tissue determines systemic fatty acid supply. A wide range of hormones and other substances have been recognized as regulators of lipolysis, but insulin and catecholamines appear to be the most important. The regulation of lipolysis, in most circumstances, provides a supply of lipid fuel exceeding the rate of lipid oxidation, requiring reesterification to triglyceride of surplus circulating free fatty acids. Thus, free fatty acid supply is usually not matched to the demand for lipid oxidation, and there is no known mechanism for accurately sensing such demand. This lax regulation may be disadvantageous in conditions such as aging, stress, obesity, and diabetes, where the antilipolytic effect of insulin is impaired and lipolysis is therefore increased. In these conditions, the surfeit of fatty acid may impair glucoregulation. In addition, the excess lipolysis may induce hypertriglyceridemia (via increased very low density lipoprotein production) and thus contribute to atherogenesis. Considerable additional research is needed in order to fully understand both normal lipolytic regulation and the abnormalities of lipolysis which accompany pathological conditions.

Adipose Tissue↗

Insulin-like growth factor-binding protein-1 response to insulin during suppression of endogenous insulin secretion.

Insulin-like growth factor-binding protein-1 (IGFBP-1) is one of several related proteins that bind and modulate the actions of IGFs. The liver is the primary source of IGFBP-1, and insulin is a major regulator of hepatic IGFBP-1 production. We report five sets of investigations that further define the characteristics of hepatic IGFBP-1 response to insulin. In normal subjects, a continuous high-dose insulin infusion caused a rapid decrease in plasma IGFBP-1 concentrations, with a rate of 0.24 +/- 0.04 microgram/L.min-1 and a t1/2 of 89 +/- 4 minutes. Conversely, a 3-hour somatostatin (SRIF) infusion caused a 4.5-fold increase in plasma IGFBP-1 levels. SRIF plus low-dose insulin infusion (to inhibit break-through insulin secretion) resulted in a plateau in IGFBP-1 concentrations at 5 to 8 hours, with a t1/2 to achieve steady state of 60 to 75 minutes. Under similar conditions, a stepped increase in plasma glucose level from 5 to 9 mmol/L had no effect on the rate of IGFBP-1 increase in plasma, indicating that an acute increase in glucose concentration within a physiologic range has no independent inhibitory effect on IGFBP-1 production in the presence of a nonsuppressive insulin level. Using SRIF plus sequential graded insulin infusions, the threshold peripheral (= portal) plasma insulin concentration for IGFBP-1 suppression was between 65 and 172 pmol/L. Subjects with insulin-dependent diabetes mellitus (IDDM) showed a similar dose-response pattern, suggesting that insulin regulation of IGFBP-1 may be normal in IDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Assessment of body composition with use of dual-energy x-ray absorptiometry: evaluation and comparison with other methods.

Dual-energy x-ray absorptiometry (DEXA) is a relatively new method of assessing body composition in humans. In the current study, DEXA was analyzed for accuracy and precision by using both anthropomorphic phantoms and a combination of body composition techniques in humans. Satisfactory precision for measurement of total body fat, fat-free mass, and total body bone mineral could be demonstrated in vivo and in vitro. Predictions of lean body mass in humans on the basis of DEXA, total body water, and total body potassium were significantly different. The results of multiple regression analysis suggested that a component of total body water was related to body potassium, and another component was predicted by body fat. In addition, extracellular fluid volume, as measured by the bromide space technique, was significantly associated with both fat-free mass and fat mass as measured by DEXA. These findings have implications for the interpretation of body composition data in humans.

Absorptiometry, Photon↗