Weight reduction increases adipose tissue lipoprotein lipase responsiveness in obese women.

Lipoprotein lipase was measured in gluteal adipose tissue from nine obese (90.6 +/- 2.7 kg) women fasting and after the intravenous infusion of insulin and glucose before, immediately after, and 3 mo subsequent to a 14.0 +/- 1.8% (mean +/- SEM) weight reduction. Fasting adipose tissue lipoprotein lipase activity (ATLPL) decreased from 5.3 to 2.3 nEq FFA/10(6) cells per min (P less than 0.02) immediately after weight reduction, yet after weight maintenance, higher levels were again found (6.1 nEq FFA/10(6) cells per min). Although responsiveness of ATLPL to 40 mU/m2 per min of insulin infusion over 6 h was absent before weight loss, increases were seen immediately after weight loss (delta 0.8, P = 0.05) and more so (delta 7.7, P less than 0.01) after 3 mo. Moreover, whereas before weight loss the ATLPL response to ingested mixed meals (delta 0.9) was minimal, in the maintained reduced-obese state a marked increase was seen (delta 12.6, P = 0.02). Thus, because ATLPL is important to lipid filling in adipose tissue, the maintenance of high levels of fasting ATLPL and the increase in enzyme responsiveness in the reduced-obese state could play an important role in the resumption of the obese state, which so commonly follows weight reduction.

Plasma lipolytic activity. Relationship to postheparin lipolytic activity and evidence for metabolic regulation.

Lipolytic activity was measured in human plasma without prior administration of intravenous heparin. Eluted from heparin-Sepharose in a barbital buffer containing 6 mg/ml heparin, plasma lipolytic activities in 20 subjects were distributed between hepatic triglyceride lipase (HTGL, mean +/- SE 60.6 +/- 4.6%) and extrahepatic lipoprotein lipase (LPL, 39.4 +/- 4.6%). Confirmation of the identities of HTGL and LPL was provided by inhibitory antisera. Preheparin LPL activity was absent in plasma from a patient with type I hyperlipoproteinemia. Both preheparin HTGL and LPL activities correlated with the respective activities measured in plasma obtained 15 min after intravenous injection of heparin (rs = + .774 and + .685, respectively; n = 12). Evidence for the metabolic regulation of preheparin lipases was provided by measurement of significant increases in LPL and HTGL activities after oral glucose ingestion. Overall, preheparin plasma HTGL and LPL activities may reflect ongoing lipoprotein lipolytic activity in tissue beds, and because these measurements do not require the administration of intravenous heparin, they should prove useful for additional studies of short-term regulation of the lipases.

Dietary substitution of medium-chain triglycerides improves insulin-mediated glucose metabolism in NIDDM subjects.

Dietary medium-chain triglycerides (MCT) may improve insulin-mediated glucose metabolism. To examine this possibility, 10 non-insulin-dependent diabetes mellitus (NIDDM) patients, 4 hypertriglyceridemic, and 6 normotriglyceridemic nondiabetic control subjects were examined with a 5-day cross-over design, in which the short-term metabolic effects of a 40% fat diet containing 77.5% of fat calories as MCT were compared with an isocaloric long-chain triglyceride-containing diet. In diabetic patients, MCT failed to alter fasting serum glucose concentrations but reduced preprandial glycemic excursions by 45% (F = 7.9, P less than 0.01). On MCT, the amount of glucose needed to maintain euglycemia during an intravenous insulin infusion was increased in diabetic subjects by 30%, in hypertriglyceridemic subjects by 30%, and in normotriglyceridemic control subjects by 17%. MCT increased mean +/- SE insulin-mediated glucose disposal (4.52 +/- 0.56 vs. 2.89 +/- 0.21 mg.kg-1.min-1; n = 3, P less than 0.05) but failed to alter basal glucose metabolism or insulin-mediated suppression of hepatic glucose output. Metabolic responses to MCT were observed independent of sulfonylurea therapy or severity of fasting hyperglycemia. No change in fasting serum insulin or triglyceride concentrations were seen with MCT administration. Although MCT increased mean fasting serum beta-hydroxybutyrate levels from 0.10 +/- 0.03 to 0.26 +/- 0.06 mM (P less than 0.05) in normotriglyceridemic nondiabetic subjects, no change was seen in diabetic patients. Thus, MCT-containing diets increased insulin-mediated glucose metabolism in both diabetic patients and nondiabetic subjects. In diabetic subjects, this effect appears to be mediated by increases in insulin-mediated glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

Fat calories may be preferentially stored in reduced-obese women: a permissive pathway for resumption of the obese state.

We previously demonstrated in unpaired studies that corn oil ingestion at the beginning of a euglycemic insulin clamp study decreased the responsiveness of gluteal adipose tissue lipoprotein lipase (ATLPL) to glucose/insulin in lean subjects. In this investigation, we performed paired euglycemic insulin clamp studies with glucose/insulin with or without oral corn oil in each of six lean [mean, 64 +/- 3 (+/- SE) kg] normal women and nine moderately obese (91 +/- 3 kg) women before and after 12.4 +/- 1.4-kg weight loss and 3 months of weight maintenance to determine if the inhibitory effect of fat calories existed in each of these states. In the obese women the fasting ATLPL activity [5.6 +/- 1.1 (+/- SE) neq FFA/10(6) cells.min] was greater than in the normal women (1.6 +/- 0.2) and did not change after weight loss and maintenance (5.0 +/- 0.7). As expected, in normal women corn oil ingestion diminished the responsiveness of ATLPL to glucose/insulin [change (delta), 0.2 +/- 0.2 vs. 3.3 +/- 0.8; P less than 0.02] during a 6-h euglycemic insulin (40 mU/m2.min) clamp. In obese women ATLPL activity did not change under either experimental condition (glucose/insulin with or without corn oil). However, after weight reduction ATLPL activity increased not only in response to glucose/insulin alone (delta, 7.7 +/- 2.4), but also in response to glucose/insulin when corn oil was ingested (delta, 7.9 +/- 2.8). Moreover, the response of ATLPL activity to glucose/insulin and corn oil was greater than that in lean women (P less than 0.05). Thus, in reduced-obese women not only did fasting ATLPL activity remain elevated and ATLPL responsiveness to glucose/insulin increase, but fat ingestion failed to blunt the ATLPL response. This inability of dietary fat to diminish the responsiveness of ATLPL to glucose/insulin and, therefore, the effect of the lipase on triglyceride deposition in adipose tissue could contribute to the resumption of the obese state that so commonly occurs after successful weight reduction.

Insulin responsiveness of adipose tissue lipoprotein lipase is delayed but preserved in obesity.

Because increases in adipose tissue lipoprotein lipase (ATLPL) may be important in the pathogenesis of obesity, the response of ATLPL to insulin during maintenance of euglycemia was examined in 22 obese and 8 normal weight subjects. Basal levels of ATLPL per g fat tissue for the obese and control groups were 18.7 +/- 2.0 (+/- SEM) and 9.6 +/- 2.7 neq/g X min, respectively. Insulin and glucose infusion rapidly produced antilipolysis in both groups, as evidenced by large falls in FFA by 20 min. When the responses of ATLPL in absolute change from basal were compared between the obese and control groups, no significant differences were found. However, because of the higher baseline ATLPL values in the obese subjects, the percent change in ATLPL from basal was significantly blunted at the 80 (P = 0.02), 180 (P less than 0.05), and 360 (P = 0.005) min timepoints compared to those in the normal subjects. By 3 h into the infusion, the control group had a significant rise in ATLPL above the basal level (4.2 +/- 1.3 ngq/g X min; P = 0.01), whereas the obese group did not (2.3 +/- 1.9 neq/g X min; P = NS). However, by 6 h, the ATLPL per g response above baseline was significantly increased in both normal (19.2 +/- 6.5 neq/g X min; P = 0.01) and obese subjects (9.8 +/- 2.3; P less than 0.001). Because adipose cell size was greater in obese subjects, data were also expressed per 10(6) cells. Basal ATLPL per 10(6) cells [11.8 +/- 1.7 neq/10(6) cells X min (obese); 3.4 +/- 0.9 neq/10(6) cells X min (normal)] was a function of cell size (rs = 0.713; P less than 0.001), body mass index (rs = 0.565; P less than 0.005), and basal insulin levels (rs = 0.434; P less than 0.05). As with the ATLPL per g response, the increases in ATLPL per 10(6) cells above basal were significant at both the 3 and 6 h marks for the normal subjects, but only at the 6 h timepoint for the obese group. Both steady state insulin levels [342 +/- 24 microU/ml (obese); 251 +/- 27 microU/ml (normal)] and the glucose infusion rates needed to maintain euglycemia [319 +/- 23 mg/m2 X min (obese); 312 +/- 33 mg/m2 X min (normal)] did not correlate with changes in ATLPL. Thus, insulin responsiveness of ATLPL in obese subjects was delayed but preserved. This phenomenon may be important in maintenance of the obese state.

Isoproterenol and somatostatin decrease plasma leptin in humans: a novel mechanism regulating leptin secretion.

In cultured adipocytes, leptin is increased by insulin and decreased by cAMP. In animal models, insulin and agents that increase intracellular cAMP have been shown to similarly affect plasma leptin in vivo. This study was undertaken to test the hypothesis that in humans increased cAMP induced by isoproterenol would decrease leptin. Five groups of normal weight subjects were studied; 1) subjects infused with isoproterenol at a rate of 24 ng/kg/min (ISO24); 2) subjects infused with isoproterenol at a rate of 8 ng/kg/min (ISO8); 3) subjects infused with somatostatin/insulin/GH followed by coinfusion with 8 ng/kg/min isoproterenol (ISO8 + SRIH); 4) subjects infused with somatostatin/insulin/GH alone (SRIH); and 5) control subjects infused with saline (NS). ISO24 infusion resulted in a 27% decrease in plasma leptin over 120 min. ISO24 also increased plasma insulin over the infusion. ISO8 resulted in a 16% decrease in leptin. Saline did not change leptin. SRIH alone decreased leptin 19% over the first 120 min, however no additional fall was seen over the next 120 min the SRIH group. Nonetheless, the addition of 8 ng/kg/min ISO during the second 120 min (ISO8 + SRIH) caused a 15% further decline in plasma leptin. Therefore both isoproterenol and somatostatin reduce plasma leptin in humans. The effect of isoproterenol is likely mediated by beta-adrenergic receptors, whereas the effect of somatostatin suggests a novel mechanism for the regulation of leptin.

Hypocaloric feeding in obese women: metabolic effects of medium-chain triglyceride substitution.

Medium-chain (MCT) and long-chain (LCT) triglyceride diets were compared during and after 4 or 12 wk of hypocaloric feeding in obese women to determine the effects on weight loss, ketones, nitrogen balance, and insulin action. After a base-line euglycemic clamp, two groups ingested an 800-kcal/d liquid diet with 30% of calories as LCT (group 1) or 6% of calories as LCT and 24% as MCT (group 2). Rate and amount of weight loss, serum ketones, and N balance were not different between groups. However, the subjects in group 2 (MCT) demonstrated an increase in glucose requirement to maintain euglycemia during the clamp after weight loss (delta 0.18 +/- 0.13 mmol.m-2.min-1) whereas subjects in group 1 (LCT) had a diminished requirement (delta -0.12 +/- 0.10, p = 0.036). Thus, an 800-kcal diet containing 24% of calories as MCT is safe and enhances insulin action but fails to increase the rate or amount of weight loss.

Effect of dietary macronutrient composition on tissue-specific lipoprotein lipase activity and insulin action in normal-weight subjects.

The effects of macronutrient composition on fasting and postprandial activities of adipose tissue lipoprotein lipase (ATLPL) and skeletal muscle LPL (SMLPL) and on insulin sensitivity (S(I)) were studied in 25 normal-weight subjects. Each subject was fed a high-carbohydrate (HC) diet for 16 d and a high-fat (HF) diet for 16 d, in randomized order. On day 15 of each diet, biopsies for ATLPL and SMLPL were done in the fasted state and 6 h postprandially. On day 16 of each diet, a euglycemic clamp was used to measure S(I). There was no effect of diet composition on fasting ATLPL or SMLPL. With both diets and in both tissues, LPL increased significantly from fasting to 6 h postprandially. In adipose tissue only there was a significant difference between the 2 diets in LPL meal response (HC >HF, P = 0.024). There was no effect of diet composition on S(I). After the HC diet only, there were significant correlations between fasting SMLPL and S(I), but not ATLPL. After the HF diet, associations between insulin action and LPL were evident only in the postprandial state. In summary, 16 d of HC compared with HF feeding in normal-weight subjects increased the responsiveness of ATLPL to an HC compared with an HF meal. However, the same diets had no effect on fasting ATLPL or SMLPL, the responsiveness of SMLPL to a meal, or S(I). These data suggest that in normal-weight subjects habitual dietary carbohydrate intake may have a stronger effect on subcutaneous fat storage than does dietary fat intake.

Regional similarities in the metabolic regulation of adipose tissue lipoprotein lipase.

Seven normal weight and 10 obese women were studied to determine the relative activities of adipose tissue lipoprotein lipase (ATLPL) in the gluteal and abdominal subcutaneous adipose tissue depots, both in the fasting state and in response to a 6-hour insulin/glucose infusion. In normal weight women, fasting gluteal enzyme activity was greater than abdominal (P less than .02). In the obese group, fasting levels of ATLPL were higher in both the gluteal and abdominal depots than in the normal weight group, but similar between regions. The regulation of ATLPL by insulin/glucose was also similar between regions in each group. When both groups were considered together, there was a strong correlation between fasting ATLPL of both regions, and between the insulin responsiveness of gluteal ATLPL and abdominal ATLPL after a 6-hour infusion. Despite regional differences in fasting ATLPL in lean women, these studies indicate that the regulation of ATLPL by insulin/glucose is largely similar in at least these two subcutaneous adipose tissue depots.

Fat feeding decreases insulin responsiveness of adipose tissue lipoprotein lipase.

The acute effect of fat feeding on the insulin-mediated stimulatory response of adipose tissue lipoprotein lipase (ATLPL) was examined in normal-weight subjects. After two days of isocaloric-formula feeding, subjects were divided into the following four groups: intravenous (IV) saline alone (sal) (n = 5), IV saline and 67 g of oral corn oil ingested at the outset of the infusion (sal/fat) (n = 5), IV insulin (40 mU/m2/min) and glucose to maintain euglycemia (ins/glu) (n = 9), and IV insulin and glucose and oral corn oil (ins/glu/fat) (n = 8). Triglycerides fell less in the ins/glu/fat group than in the ins/glu group (0 +/- 8% v 35 +/- 5%, means +/- SEM, at three hours, P less than 0.01; 15 +/- 8% v 43 +/- 6% at six hours, P less than 0.02). ATLPL in the sal and sal/fat groups did not change during the six-hour period. When the responsiveness of ATLPL was compared between ins/glu/fat subjects and ins/glu subjects, decreases were seen at both three and six hours (-0.3 +/- 3.0 v 15.1 +/- 5.4 nEq/g/min, P less than 0.05; 6.7 +/- 2.7 v 27.9 +/- 3.9 nEq/g/min, P less than 0.001). The glucose infusion rates needed to maintain euglycemia were also decreased by fat feeding, 229 +/- 18 v 287 +/- 20 mg/m2/min (P less than 0.05). Thus, fat feeding with insulin and glucose infusions diminishes the insulin responsiveness of ATLPL.(ABSTRACT TRUNCATED AT 250 WORDS)

Glycohemoglobin levels relate to the response of adipose tissue lipoprotein lipase to insulin/glucose in obese non-insulin-dependent diabetes mellitus.

Adipose tissue lipoprotein lipase (ATLPL) is responsible for the provision of lipoprotein-derived fatty acids to adipocytes for storage as triglycerides. Fasting ATLPL has been shown to be decreased in non-insulin-dependent diabetes mellitus (NIDDM), an insulin-resistant state. Medically uncomplicated obesity, another state of relative insulin resistance, is associated with decreased stimulation of the enzyme in response to metabolic stimuli. It was therefore hypothesized that the increased insulin resistance of NIDDM would result in an even greater defect in the response of ATLPL to insulin/glucose. Gluteal adipose tissue biopsies were performed in 13 premenopausal obese women with NIDDM, before and after 6 hours of intravenous insulin and glucose. Metabolic data from these studies were then compared with those obtained from 26 nondiabetic obese women of similar age, weight, and fasting insulin concentration (obese controls [OBC]). As expected, fasting gluteal ATLPL activity was lower in the NIDDM group than in OBC (3.7 +/- 0.9 v 11.1 +/- 1.6 nmol free fatty acids [FFA]/min/10(6) cells, P = .0003). The change in ATLPL activity (delta ATLPL) in response to a 6-hour insulin/glucose infusion was not statistically different between the two groups (2.2 +/- 1.1 v 4.7 +/- 1.2, P = .114). However, in NIDDM subjects there was a strong positive relationship between delta ATLPL and glycohemoglobin (GHb) level (r = .883, P = .0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue-specific regulation of lipoprotein lipase activity by insulin/glucose in normal-weight humans.

Eight normal-weight subjects (four men, four women) were studied to determine the relative activities of lipoprotein lipase (LPL) in adipose tissue (ATLPL) and vastus lateralis skeletal muscle (SMLPL), both in the fasting state and in response to a 6-hour insulin/glucose infusion. Mean fasting levels of ATLPL and SMLPL were not statistically different. After 6 hours of insulin/glucose infusion, mean ATLPL activity was significantly greater than the fasting level (P less than .01), while mean SMLPL activity decreased from basal (P less than .05). These tissue-specific changes in LPL responsiveness (0 to 6 hours) were significantly different (P less than .01). No differences between men and women were observed. These divergent tissue-specific LPL responses to insulin/glucose would serve to direct lipoprotein triglyceride-derived fatty acids away from muscle and to adipose tissue for storage.

Change in skeletal muscle lipoprotein lipase activity in response to insulin/glucose in non-insulin-dependent diabetes mellitus.

Skeletal muscle lipoprotein lipase (SMLPL) provides fatty acids to myocytes for lipoprotein triglyceride oxidation. In human obesity, an insulin-resistant state, SMLPL levels measured in the fasted state are either decreased or unchanged as compared with levels in normal-weight controls. However, insulin/glucose infusion increases SMLPL activity in obese individuals, whereas in normal-weight subjects the activity is decreased. One of the goals of this study was to determine the impact of obesity with concomitant non-insulin-dependent diabetes mellitus (NIDDM) on fasting SMLPL and on the change in SMLPL activity (delta MLPL) in response to an insulin/glucose infusion. Because NIDDM is often a more insulin-resistant state, it was hypothesized that SMLPL activity would be further increased by insulin/glucose in subjects who were obese and had NIDDM. Measurements of SMLPL were made from biopsies of vastus lateralis skeletal muscle taken before and after a 6-hour insulin/glucose infusion in the setting of a euglycemic clamp. Thirteen nondiabetic obese women (OBC) and six nondiabetic normal-weight women (NWC) were used as control subjects. SMLPL levels measured in the fasted state were significantly lower in obese NIDDM subjects as compared with either control group. Relative insulin action was determined by calculation of the mean glucose infusion rate (GIR) required to sustain euglycemia over the last 60 minutes of the infusion. For all three groups combined, representing a continuum of insulin sensitivity, there was a positive correlation between GIR and fasting SMLPL. As described earlier, in the NWC group SMLPL activity decreased significantly after 6 hours of insulin/glucose, and in the OBC group SMLPL increased after insulin/glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Suction lipectomy: outcome relates to region-specific lipoprotein lipase activity and interval weight change.

To determine the effects of suction lipectomy on regional adipose tissue metabolism, nine women had repetitive circumferential measurements and biopsies of subcutaneous adipose tissue from a lipectomy site (site A) and a nonlipectomy site (site B) up to 12 months following lipectomy. Maximum reductions from preoperative baseline in weight, body mass index, and circumferences of sites A and B occurred at 3 months. Because of variable long-term compliance (6 to 12 months), we created a "last visit" time-point to assess adequately the effects of lipectomy for each individual. Not all subjects maintained reduction in site circumferences from 3 months to the last visit. The change in circumference of site A for that period was highly correlated with the change in circumference of site B (r = 0.828, p = 0.005). The change in circumference of site B, but not site A, at 3 months was related to the weight change above the weight of adipose tissue removed at suction lipectomy. Five subjects who were "sustained responders" to the lipectomy procedure were able to maintain or decrease circumferences of sites A and B from 3 months to the last visit. In contrast, four "limited responders" actually increased circumference of site A and had either no change or increased circumference of site B from 3 months to the last visit. The changes in circumference in both sites between 3 months and the last visit related to changes in body weight over the same interval. Ultimately, the decrement in circumference of site A was 3.4 percent (-2.4 cm) greater than that of site B (p = 0.0001). The response to lipectomy in site B, but not site A, between 3 months and the last visit was related to the change in fasting adipose tissue lipoprotein lipase from baseline to 3 months (r = 0.728, p = 0.026). This change in lipase activity in the control region may represent a metabolic defense of body weight in response to adipose tissue removal in the lipectomy site.

HDL subfractions and adipose tissue metabolism in the reduced-obese state.

The effect of weight reduction on fasting serum lipids and lipoproteins and adipose tissue lipoprotein lipase responsiveness to insulin was assessed immediately after and 3 mo subsequent to a mean 11.7% weight reduction in 14 women. Whereas reduction in fasting serum triglycerides persisted after 3 mo, reductions in serum cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein (HDL) cholesterol were not found at 3 mo. In fact, at 3 mo, levels of HDL cholesterol were higher than before weight reduction. Maintenance of the reduced-obese state also increased the HDL2-to-HDL3 cholesterol ratio (P less than 0.01), an effect strongly associated with the change in the responsiveness of adipose tissue lipoprotein lipase to insulin (r = 0.821, P less than 0.001). Moreover, after maintenance of the reduced-obese state, the HDL2-to-HDL3 cholesterol ratio also increased after the ingestion of corn oil and a 6-h insulin-glucose infusion, a response not present before weight reduction. Thus the effect of weight reduction on serum lipids and lipoproteins was not only time dependent, but for HDL, was strongly associated with changes in adipose tissue metabolism.

Deficiency of the insulin, glucose-mediated decrease in serum triglycerides in normolipidemic obese subjects.

The effects of a 6-h insulin, glucose infusion on lipid metabolism were compared in 29 normolipidemic obese and 20 control subjects. Alterations in serum triglycerides (TG), cholesterol, and high-density lipoprotein (HDL) cholesterol were similar within groups when either 40 or 120 mU/m2 per min of regular insulin were infused. Although changes in the HDL cholesterol responses to the insulin, glucose infusions were also similar in obese and control subjects, TG fell more in insulin, glucose-infused controls (35 +/- 4 mg/dl, means +/- s.e.m.) than obese subjects (23 +/- 3) (P less than 0.001). The rate and magnitude of the insulin, glucose-mediated fall in free fatty acids, however, were not different between the two groups. This diminished responsiveness of TG to an insulin, glucose infusion in normotriglyceridemic obese subjects is another manifestation of the insulin resistance of obesity.

Preheparin lipoprotein lipolytic activities: relationship to plasma lipoproteins and postheparin lipolytic activities.

To determine the putative metabolic relevance of preheparin versus postheparin lipoprotein lipases, the relationships of both pre- and postheparin lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) to plasma triglycerides, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol were determined in 93 men. Relationships of preheparin lipases to their respective postheparin lipases were also examined. Although relationships between the preheparin lipases and plasma triglycerides and HDL cholesterol were not apparent, both preheparin LPL (rs = 0.306, P = 0.0036) and HTGL (rs = 0.348, P = 0.0008) correlated with LDL cholesterol, a relationship not seen with either postheparin lipase. Both postheparin LPL (rs = 0.515, P = 0.0001) and postheparin HTGL (rs = -0.228, P = 0.0028), however, correlated with HDL cholesterol. In addition, postheparin LPL was inversely correlated with postheparin HTGL (rs = -0.363, P = 0.0003), whereas the relationship between preheparin LPL and preheparin HTGL was positive (rs = 0.228, P = 0.0009). Overall, these data point to differences between pre- and postheparin lipases in their relationships to lipoproteins, and one to another. The relationships of LDL cholesterol to both preheparin LPL and HTGL suggest that displacement of active forms of both lipases from their endothelial binding sites may mark triglyceride-rich lipoproteins or their remnants for metabolic pathways that lead to LDL.

Weight regain following sustained weight reduction is predicted by relative insulin sensitivity.

Ten moderately obese women (body mass index 34.9 +/- 1.1 kg/m2, mean +/- SEM), had previously been through a 3-month weight loss program followed by 3 months of weight maintenance at the reduced weight. A euglycemic clamp for determination of insulin sensitivity was performed on each subject prior to weight loss, and another at the end of the weight maintenance phase. The mean weight loss for the group was 11.4 +/- 2.2 kg. The women were then seen for follow-up weights 12 months and 18 months after the conclusion of the weight maintenance period. All of the women except one had regained their weight by the time of the 12-month visit. It was found that the amount of weight regained both at 12 months and 18 months was correlated with the change in insulin sensitivity which occurred from the baseline study to after weight loss/maintenance. The data indicate that increased insulin sensitivity following sustained weight loss in obese women predicts weight regain.

Sustained weight reduction in moderately obese women results in decreased activity of skeletal muscle lipoprotein lipase.

Obesity is an increasingly prevalent problem, and long-term maintenance of the weight-reduced state is difficult for the obese individual. Following weight reduction, many metabolic changes occur. Among these is an increase in adipose tissue lipoprotein lipase (ATLPL), which predicts an alteration in lipid fuel partitioning which may then contribute to resumption of the obese state. The purpose of this study was to test whether changes in skeletal muscle LPL (SMLPL) and its response to insulin/glucose after sustained weight reduction also indicate a potential altered partitioning of lipid fuels away from oxidative pathways in muscle to storage in adipose tissue. Biopsies of vastus lateralis muscle were carried out in premenopausal obese women (n = 11, 94 +/- 4 kg, mean +/- SEM) before and after consumption of a 900 kcal day-1 diet for 3 months followed by 3 months of isocaloric maintenance of the reduced weight (n = 11, 82 +/- 4 kg). SMLPL activity was measured in the fasted state and after 6 h insulin/glucose infusion, before and after sustained weight loss. SMLPL activities were also measured in six normal weight women. Fasting SMLPL activity in obese women (3.9 +/- 0.3 nmol FFA min-1 g-1) was similar to that measured in normal weight control women (4.4 +/- 0.5). Unlike normal weight controls in whom a 6 h insulin/glucose infusion decreased SMLPL activity, in obese women the response of SMLPL was positive (normal weight vs. obese: delta -0.8 +/- 0.3 vs. delta 1.6 +/- 0.5, P = 0.002). Following maintained weight reduction, fasting SMLPL in the obese group was reduced to 1.2 +/- 0.3 (obese before weight loss vs. obese after: P = 0.0001). This change in fasting SMLPL activity following weight loss/maintenance correlated with the resultant change in percent body fat (r s = 0.663, P = 0.026).(ABSTRACT TRUNCATED AT 250 WORDS)

Tissue-specific lipoprotein lipase: relationships to body composition and body fat distribution in normal weight humans.

Twenty-six normal weight subjects (22 female, 4 male) were studied to determine the relationships of fasting levels of lipoprotein lipase in gluteal adipose tissue (ATLPL) and skeletal muscle (SMLPL) to body composition and body fat distribution. No relationship was found between fasting gluteal ATLPL and percent (%) body fat. There was, however, an inverse relationship between fasting SMLPL (from the vastus lateralis) and %body fat (p=0.005). A strong inverse correlation was also seen between fasting ATLPL and waist/hip ratio (p=0.0006), a measurement of body fat distribution. These relationships existed with or without the male subjects included. The tissue-specific relationships of lipoprotein lipase to body composition and body fat distribution could relate to the development of obesity or the maintenance of normal body weight by the effects of the lipase on the partitioning of lipoprotein triglyceride fatty acids.