Biomedical subjects

R V Considine

Publications and source records attributed to R V Considine.

At least 37 records · Page 2Linked to original sources

PubMed1998

Relationship of leptin concentration to gender, menopause, age, diabetes, and fat mass in African Americans.

This investigation was designed to determine the relationship of leptin concentration to gender, sex hormones, menopause, age, diabetes, and fat mass in African Americans. Participants included 101 African Americans, 38 men (mean age, 34.2 +/- 7.4 years), 29 age-matched premenopausal women (mean age, 32.6 +/- 3.7 years), and 36 postmenopausal women (mean age, 57.8 +/- 5.9 years). The women were not taking exogenous sex hormones, and 12 subjects were diabetic. Percent body fat was calculated with the Siri formula, fat mass (FM) was calculated as weight x percent body fat, and Fat-free mass (FFM) was calculated as weight minus FM. Fasting plasma was assayed for leptin, estradiol, free testosterone, glucose, and insulin concentrations. The nondiabetics had an oral glucose tolerance test (OGTT). The diabetics compared with the non-diabetics had a higher central fat index (p=0.04) but otherwise were similar to nondiabetics in all parameters measured. Body mass index, percent body fat, and FM were greater in women than men (p<0.001). Leptin concentrations in men, premenopausal, and postmenopausal women were: 7.51 +/- 8.5, 33.9 +/- 17.3, 31.4 +/- 22.3 ng/mL. Leptin/FM x 100 in the three groups were: 28.9 +/- 16.1, 98.65 +/- 44.9, 77.1 +/- 44.5 ng/mL/kg. The gender difference in leptin concentration and leptin/FM was significant (p<0.001), but the difference between premenopausal and postmenopausal women was not. In each group, weight, percent body fat, and FM were highly correlated with leptin concentration. Multiple regression analyses with leptin concentration as the dependent variable and age, diabetic status, percent body fat, weight, FM, FFM, estradiol, and free testosterone concentrations as independent variables demonstrated that the determinants of leptin concentration in men was weight only (R=0.83, p<0.001), in premenopausal women it was FM only (R=0.57, p<0.001), and in postmenopausal women it was weight only (R=0.67, p<0.001). With diabetics excluded, the multiple regression analysis was repeated with fasting insulin concentration and the area under the insulin curve during the OGTT included as independent variables. The results for this multiple regression analyses were the same as the first. Therefore, leptin concentration in African Americans is determined by gender and fat mass. Menopause, age, and diabetes do not affect leptin concentration.

Adult↗

PubMed1998

Acute changes in free-fatty acids (FFA) do not alter serum leptin levels.

Adult↗

PubMed1998

Effect of hydrolyzed guar fiber on fasting and postprandial satiety and satiety hormones: a double-blind, placebo-controlled trial during controlled weight loss.

OBJECTIVE: To evaluate the effects of a completely soluble fiber on fasting and postprandial hormone levels, respiratory quotient (RQ) and subjective ratings of satiety during a controlled weight-loss program. DESIGN: In a five-week prospective, randomized, double-blind study, a 3.3 MJ (800 kcal)/d diet was provided during a two-week wash-in period. Then, during the intervention weeks, separated by a one-week wash-out period, a 3.3 MJ (800 kcal) formula containing either 20 g fiber or placebo daily, was given in a cross-over design and on days 1, 3 and 7 of the intervention weeks (weeks 3 and 5) measurements were taken after an overnight fast. SUBJECTS: 25 obese but otherwise healthy females (age: 46+/-6 y, body mass index (BMI): 35+/-6 kg/m2) were studied. MEASUREMENTS: Body weight; hunger/satiety ratings; glucose, insulin, cholecystokinin (CCK) and leptin concentrations; RQ during the intervention weeks. RESULTS: In the fasting state, the supplement had no effect on any of the measured parameters, including blood concentrations of glucose, insulin, CCK, and leptin, RQ and satiety ratings. In the 2 h postprandial period following the test meal, none of the measured parameters differed significantly from that following the non-fiber-supplemented meal, except for the CCK response. CCK demonstrated an overall higher concentration after the fiber-supplemented meal (P=0.007), even after adjustment for age, weight, height and treatment sequence. The postprandial peak in CCK also occurred earlier (at 15 min vs 30 min) after completion of the fiber-supplemented meal. CONCLUSIONS: The results indicated that a hydrolyzed guar gum fiber supplement produced a heightened postprandial CCK response, but did not alter other satiety hormones or increase satiety ratings, in either the fasting or the postprandial state.

Adult↗

PubMed1998

Association of leptin and hunger-satiety ratings in obese women.

OBJECTIVE: To measure leptin, insulin and cholecystokinin (CCK) concentrations in obese women on calorie restriction and to determine their correlation with hunger-satiety ratings. Although it has been proposed to play a role in appetite regulation, the effects of physiological concentrations of these hormones on hunger-satiety in humans have not yet been well established. DESIGN: Prospective metabolic study. A two week 'wash-in period' followed by a three-week observation period, during which each subject underwent six measurements of satiety, blood parameters and body weight. SETTING: Energy Metabolism Research Unit, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. SUBJECTS: 22 moderately to severely overweight women (mean age: 45 +/- 8 y; body mass index (BMI): 33 +/- 6 kg/m2). INTERVENTION: Energy restriction, in the form of a 3.3 MJ (800 kcal) diet during five weeks. MAIN OUTCOME MEASUREMENTS: Fasting blood levels of leptin, insulin, glucose and CCK, fasting hunger-satiety scores and body weight. RESULTS: The mean (+/- s.d.) fasting serum leptin concentration at the beginning of the observation period was 26.1 +/- 15.9 ng/ml (range: 6.7-59.8 ng/ml). Leptin concentrations correlated positively with body weight (P < 0.0001). Furthermore, reductions in body weight were associated with decreases in fasting leptin levels (P = 0.002). Leptin concentrations correlated with serum levels of insulin (P = 0.0001) and CCK (P = 0.06), but in multivariate analysis including insulin, CCK and glucose, only leptin had a significant relationship with satiety (P = 0.04). This relationship was linear. CONCLUSIONS: These results confirm the association between leptin levels, body weight and serum insulin. We also showed that higher serum leptin levels correlated with greater feelings of fullness, a relationship which was not blunted in the more obese subjects. These findings suggest that leptin is a satiety hormone that reduces appetite, even in obese individuals, and that weight gain must be due to other factors, overriding this feed-back regulation.

Adult↗

PubMed1998

The Ob protein (leptin) and the kidney.

Mutation of the Ob gene, which encodes for leptin, or mutation of the leptin receptor leads to obesity in mice. Humans, for the most part, have a positive correlation of leptin with body fat mass suggesting possible defects in leptin effector mechanisms that may contribute to obesity. As patients on hemodialysis have difficulty with appetite, we investigated whether leptin is cleared by the kidney and is elevated in hemodialysis patients. In patients with intact renal function there was a net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there was no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal disease (ESRD), peripheral leptin levels factored for body mass index was increased by fourfold as compared to a group of healthy controls (N = 338). The leptin receptor exists in a long and short form, with the long form primarily expressed in the hypothalamus but also in the lungs and kidneys of the mouse. Further studies are necessary to clarify the role of leptin in regulating appetite in patients with ESRD and the role of leptin in directly affecting kidney function via its receptors.

Animals↗

PubMed1998

A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?

SUMMARY BACKGROUND DATA: We previously reported, in a study of 608 patients, that the gastric bypass operation (GB) controls type 2 diabetes mellitus in the morbidly obese patient more effectively than any medical therapy. Further, we showed for the first time that it was possible to reduce the mortality from diabetes; GB reduced the chance of dying from 4.5% per year to 1% per year. This control of diabetes has been ascribed to the weight loss induced by the operation. These studies, in weight-stable women, were designed to determine whether weight loss was really the important factor. METHODS: Fasting plasma insulin, fasting plasma glucose, minimal model-derived insulin sensitivity and leptin levels were measured in carefully matched cohorts: six women who had undergone GB and had been stable at their lowered weight 24 to 30 months after surgery versus a control group of six women who did not undergo surgery and were similarly weight-stable. The two groups were matched in age, percentage of fat, body mass index, waist circumference, and aerobic capacity. RESULTS: Even though the two groups of patients were closely matched in weight, age, percentage of fat, and even aerobic capacity, and with both groups maintaining stable weights, the surgical group demonstrated significantly lower levels of serum leptin, fasting plasma insulin, and fasting plasma glucose compared to the control group. Similarly, minimal model-derived insulin sensitivity was significantly higher in the surgical group. Finally, self-reported food intake was significantly lower in the surgical group. CONCLUSIONS: Weight loss is not the reason why GB controls diabetes mellitus. Instead, bypassing the foregut and reducing food intake produce the profound long-term alterations in glucose metabolism and insulin action. These findings suggest that our current paradigms of type 2 diabetes mellitus deserve review. The critical lesion may lie in abnormal signals from the gut.

Adult↗

PubMed1998

Interaction between leptin and neuropeptide Y on in vivo growth hormone secretion.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. Leptin has recently been shown to play a stimulatory role on GH secretion. The aim of the present study was to investigate whether leptin regulation of GH secretion was mediated by hypothalamic neuropeptide Y (NPY). We assessed the effect of leptin administration (10 microg, i.c.v.) and/or NPY (4 microg, i.c. v.) on fasted rats. Furthermore we administered leptin antiserum (10 microl, i.c.v.), anti-NPY serum (5 microl, i.c.v.) or normal rabbit serum (10 microl, i.c.v.) to freely moving fed rats. Spontaneous GH secretion was assessed over 6 h with blood samples taken every 15 min. Fed rats treated with anti-NPY serum exhibited a normal ultradian GH rhythm. However, administration of anti-NPY serum (5 microl, i.c.v., at 120 min) completely reversed the suppression induced by antileptin serum (10 microl, i.c.v., at 0 min) on plasma GH levels (area under the curve, AUC, 168 +/- 72 vs. 1,287 +/- 430 ng/ml/6 h; p < 0.01). In fasted rats, following NPY administration, GH levels remained suppressed throughout the 6 h studied. Besides, NPY administration completely blunted leptin-induced GH secretion as assessed by the AUC (28.5 +/- 11 vs. 520 +/- 220 ng/ml/6 h; p < 0. 01). Thus, it is possible that NPY mediates the effects of leptin on GH secretion. Alternatively, leptin and NPY could act through parallel pathways to alter GH release with NPY overcoming the stimulatory effect exerted by leptin on plasma GH levels.

Animals↗

PubMed1998

Short- and long-term changes in serum leptin dieting obese women: effects of caloric restriction and weight loss.

This study examined the effects of caloric restriction and weight loss on serum leptin concentrations in 49 obese women who participated in a 40-week weight loss program. During the first 12 weeks, half the subjects were provided a 1000 kcal/day low-calorie diet (LCD), compromised of portion-controlled foods, whereas the other half were prescribed a 1200 kcal/day balanced deficit diet (BDD) consisting of self-selected table foods. Thereafter, subjects in both conditions were instructed to consume approximately 1200-1800 kcal/day of self-selected foods, depending on their desired weight change. During the first 6 weeks, weight and serum leptin fell significantly more (P < 0.05) in women in the LCD condition than in the BDD condition. In the former group, the 55% reduction in baseline leptin was 10 times greater than the relative reduction in body weight. Stepwise multiple regression analysis revealed that degree of caloric restriction, but not weight loss, contribution significantly to the variance in the change in leptin at week 6. By contrast, long-term changes in leptin, when subjects had increased their calorie intake, were more strongly related to changes in weight and fat. At week 40, for example, weight loss account for 47% of the variance in the change in leptin. Serum leptin and body fat remained highly correlated after weight loss (r = 0.79, P < 0.001), as before (r = 0.66, P < 0.001). After treatment, however, we observed a greater-than-expected reduction in serum leptin concentrations, as expressed per kilogram of body fat. The significance of this finding remains to be determined.

Adipose Tissue↗

PubMed1998

Effect of obesity on estradiol level, and its relationship to leptin, bone maturation, and bone mineral density in children.

The purpose of this study was to investigate 24-h estradiol and leptin levels in obese and nonobese children to further understand the roles of estradiol and leptin in obesity and puberty. We measured serum estradiol, leptin, insulin, glucose, and GH levels every hour for 24 h in 18 obese (12 females and 6 males) and 30 nonobese (11 females and 19 males) prepubertal and early pubertal (stages 1-2) children. Bone age and dual energy x-ray absortiometry (DEXA) were obtained upon completion of the 24-h study. Obese children were significantly younger than nonobese children, with no difference in pubertal stage, height, or bone age between the 2 groups. Obese children had greater bone age to chronological age ratios than nonobese children, indicating a more advanced rate of bone maturation. Mean 24-h estradiol levels correlated significantly with chronological age and bone age as well as with insulin-like growth factor I, insulin-like growth factor-binding protein-3, dehydroepiandrosterone sulfate, mean 24-h GH, and lean body mass. Mean 24-h estradiol levels did not differ between obese and nonobese children [1.65+/-1.47 us. 2.75+/-3.30 pmol/L (0.45+/-0.40 vs. 0.75+/-0.90 pg/mL), respectively]. Similar mean 24-h estradiol levels in obese and nonobese children are consistent with the increased bone maturation of the obese children. Estradiol did not correlate significantly with DEXA fat mass, body mass index, or arm fat measures of adiposity. Obese children had higher 24-h mean leptin concentrations than nonobese children (28.6+/-17.4 vs. 6.8+/-7.1 ng/mL; P < 0.001). Leptin concentrations positively correlated with DEXA fat mass, body mass index, and arm fat measurement of adiposity. Girls had higher 24-h mean leptin levels than boys when controlling for adiposity. Estradiol and leptin concentrations fluctuated over a 24-h period in both groups, with all children having higher leptin concentrations at night and higher estradiol concentrations in the morning. This diurnal rhythm was of a similar pattern, but at higher levels for leptin and lower levels for estradiol in the obese children compared to nonobese children. There was no significant correlation between estradiol and leptin levels. Bone mineral density, as measured by DEXA, did not differ between obese and nonobese children. Similar bone mineral density values in obese and nonobese children are consistent with the increased bone maturation of the obese children. Bone mineral density was not correlated with estradiol or leptin level in these children. In conclusion, obese children had similar estradiol levels and equivalent bone ages at a younger chronological age than nonobese children. Leptin was higher in these obese children, but did not correlate with estradiol level or bone age. These findings suggest that the role of leptin in both obesity and pubertal development is not directly correlated with the estradiol level.

Bone Density↗

PubMed1998

Serum leptin levels and energy expenditure in normal weight women.

To investigate whether circulating leptin levels are associated with energy expenditure in healthy humans, doubly labeled water energy measurements and food intake assessment were carried out in 27 women (mean age, 48.6 years; weight, 61.9 kg; body mass index, 23.2). Energy expenditure was determined over 13 days. Food intake was measured by 7-day food records. Leptin was measured by radioimmunoassay. Leptin level was strongly associated with percentage body fat (r = 0.59; p < 0.001), fat mass (r = 0.60; p < 0.001), and body mass index (r = 0.41; p = 0.03), but no correlation was observed with energy expenditure (r = 0.02; p = 0.93). After controlling for percentage body fat, a positive association of leptin level with energy expenditure of marginal significance (p = 0.06) was observed. There were no significant univariate associations of age, physical activity, lean body mass, height, or dietary variables with leptin level. When controlling for body fat, a significant positive correlation was observed for percent energy from carbohydrate and negative correlations with dietary fat and alcohol intake. These findings confirm previous associations between leptin and body fat content and suggest a relationship between serum leptin and energy expenditure level in healthy humans.

Body Weight↗

PubMed1997

Peroxisome proliferator-activated receptor gene expression in human tissues. Effects of obesity, weight loss, and regulation by insulin and glucocorticoids.

The peroxisome proliferator activated receptor (PPAR gamma) plays a key role in adipogenesis and adipocyte gene expression and is the receptor for the thiazolidinedione class of insulin-sensitizing drugs. The tissue expression and potential for regulation of human PPAR gamma gene expression in vivo are unknown. We have cloned a partial human PPAR gamma cDNA, and established an RNase protection assay that permits simultaneous measurements of both PPAR gamma1 and PPAR gamma2 splice variants. Both gamma1 and gamma2 mRNAs were abundantly expressed in adipose tissue. PPAR gamma1 was detected at lower levels in liver and heart, whereas both gamma1 and gamma2 mRNAs were expressed at low levels in skeletal muscle. To examine the hypothesis that obesity is associated with abnormal adipose tissue expression of PPAR gamma, we quantitated PPARgamma mRNA splice variants in subcutaneous adipose tissue of 14 lean and 24 obese subjects. Adipose expression of PPARgamma 2 mRNA was increased in human obesity (14.25 attomol PPAR gamma2/18S in obese females vs 9.9 in lean, P = 0.003). This increase was observed in both male and females. In contrast, no differences were observed in PPAR gamma1/18S mRNA expression. There was a strong positive correlation (r = 0.70, P < 0.001) between the ratio of PPAR gamma2/gamma1 and the body mass index of these patients. We also observed sexually dimorphic expression with increased expression of both PPAR gamma1 and PPAR gamma2 mRNAs in the subcutaneous adipose tissue of women compared with men. To determine the effect of weight loss on PPAR gamma mRNA expression, seven additional obese subjects were fed a low calorie diet (800 Kcal) until 10% weight loss was achieved. Mean expression of adipose PPAR gamma2 mRNA fell 25% (P = 0.0250 after a 10% reduction in body weight), but then increased to pretreatment levels after 4 wk of weight maintenance. Nutritional regulation of PPAR gamma1 was not seen. In vitro experiments revealed a synergistic effect of insulin and corticosteroids to induce PPAR gamma expression in isolated human adipocytes in culture. We conclude that: (a) human PPAR gamma mRNA expression is most abundant in adipose tissue, but lower level expression of both splice variants is seen in skeletal muscle; to an extent that is unlikely to be due to adipose contamination. (b) RNA derived from adipose tissue of obese humans has increased expression of PPAR gamma 2 mRNA, as well as an increased ratio of PPAR gamma2/gamma1 splice variants that is proportional to the BMI; (c) a low calorie diet specifically down-regulates the expression of PPAR gamma2 mRNA in adipose tissue of obese humans; (d) insulin and corticosteroids synergistically induce PPAR gamma mRNA after in vitro exposure to isolated human adipocytes; and (e) the in vivo modulation of PPAR gamma2 mRNA levels is an additional level of regulation for the control of adipocyte development and function, and could provide a molecular mechanism for alterations in adipocyte number and function in obesity.

Adipose Tissue↗

PubMed1997

Dexamethasone stimulates leptin release from human adipocytes: unexpected inhibition by insulin.

In the present study we have examined the effect of dexamethasone on ob gene mRNA expression and leptin release from isolated human subcutaneous adipocytes. Dexamethasone stimulated leptin release from cultured adipocytes in a time- and dose-dependent manner. A two-fold increase in leptin release was detectable by 36 h of treatment with 10(-7) M dexamethasone. Leptin release was preceded by a significant 83 +/- 30% increase in ob mRNA after 24 h exposure to the compound. Co-incubation of cells with dexamethasone (10(-7) M) and insulin (10(-7) or 10(-9) M) completely blocked the dexamethasone-stimulated increase in ob mRNA and leptin release. These data demonstrate that insulin and glucocorticoids regulate leptin synthesis and release from human adipocytes in vitro.

Adipocytes↗

PubMed1997

Serum immunoreactive leptin concentrations in patients with anorexia nervosa before and after partial weight recovery.

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes. Serum leptin concentrations increase in correlation with the percentage of body fat, but besides that little is known about the physiological actions of leptin in humans. In order to understand the role of leptin in severe malnutrition, in the present work 10 patients recently diagnosed with anorexia nervosa were studied both before and 2 months later, after partial weight recovery, and were compared with 18 normal-weight women as controls. Leptin was measured by a newly developed radioimmunoassay and both IGF-I and IGFBP-3 were measured by commercial radioimmunoassays. The mean (+/-SE) serum leptin concentrations (in microgram/liter) were 18.1 +/- 2.0 in control women with BMI of 21.1 +/- 0.3, significantly higher (P < 0.01) than that in the anorexia nervosa patients at diagnosis (2.2 +/- 0.1, BMI 15.3 +/- 0.6). These differences were also observed in IGF-I values (microgram/liter) that were 228.0 +/- 14.6 in controls and 157.4 +/- 28.7 in anorexia nervosa patients (P < 0.02). No differences were observed in IGF-BP3. After treatment, patients with anorexia nervosa experienced an increase in BMI (17.1 +/- 0.5, P < 0.0001 vs before) although they were still underweight. The partial recovery in weight led to a complete normalization of IGF-I levels (214.0 +/- 21.0 micrograms/liter) and to an enhancement in leptin levels (3.3 +/- 0.5 micrograms/liter; P < 0.03 vs before treatment), though still lower than those in normal-weight women (P < 0.05). Individually analyzed, a large dispersion was observed in control subjects, with leptin levels ranging from 5.5 to 38.7 micrograms/liter, while in all anorexia nervosa patients leptin levels were under 3 micrograms/liter. A treatment-induced increase in body weight led to an increase in leptin levels in 7 out of the 10 anorexia nervosa patients studied and the 3 patients with no increase in leptin were all initially under the 14.5 BMI. In conclusion, leptin levels are severely reduced in anorexia nervosa patients with severe malnutrition, and a significant rise occurred after partial weight recovery. There seems to be a level of BMI below which leptin levels do not drop further but also do not increase despite weight gain. While IGF-I reflects the energy intake of the previous few weeks, the serum leptin concentration reflects the true status of the adipose stores, a fact that has useful clinical implications.

Adult↗

PubMed1997

Leptin and obesity in humans.

It now appears that leptin is the peripheral signal, hypothesized in the lipostasis theory, that informs the central nervous system how much adipose tissue there is in the body. The ability of the leptin signal to regulate body composition and the amount of body fat has been demonstrated in animals. Furthermore, defects in the ob gene and the leptin receptor lead to the development of obesity in rodents. No such defects have been found in humans although it appears that obese humans are resistant to the action of their endogenous leptin. Further characterization of the hormone and ultimately, the administration of leptin to humans, will be necessary to determine the role of the leptin signal system in the development of obesity in humans.

Adipose Tissue↗

PubMed1997

Leptin plasma levels in healthy Spanish children and adolescents, children with obesity, and adolescents with anorexia nervosa and bulimia nervosa.

OBJECTIVES: (1) To investigate normal circulating levels of leptin in children at various stages of pubertal maturation (Tanner stages) according to sex; and (2) to analyze serum leptin levels in pediatric patients with eating disorders (obesity, anorexia nervosa, and bulimia nervosa). STUDY DESIGN: Fasting leptin levels were studied in normal healthy boys and girls throughout development. Obese pediatric subjects and patients with anorexia nervosa were studied at the time of diagnosis and after 6 months and 1 year of treatment for weight reduction or weight recuperation, respectively. Patients with bulimia nervosa were studied at the moment of diagnosis. RESULTS: Leptin levels in both boys and girls vary significantly depending on the maturational stage, being low in both sexes at Tanner stage I and rising significantly by Tanner stage III. In girls, there was a further increase by Tanner stage V and a significant decrease in boys, resulting in a sexual dimorphism in Tanner V subjects. In obese prepubertal patients, leptin levels were significantly elevated at the time of diagnosis and declined significantly with weight loss (ANOVA: p < 0.0001). In anorexia nervosa patients' leptin levels are significantly reduced compared with age- and sex-matched controls (p < 0.0001). These levels remain significantly lower even after recovery of at least 10% of the original body weight and 1 year later. In patients with bulimia leptin levels were reduced at the time of diagnosis but were significantly higher than in patients with anorexia. CONCLUSION: In normal pediatric subjects leptin levels are highly correlated with the body mass index, but this is not the case in eating disorders, where the body mass index is either significantly elevated or reduced. Both age and sex should be taken into consideration when analyzing serum leptin levels.

Adolescent↗

PubMed1997

Improved sensitivity to insulin in obese subjects following weight loss is accompanied by reduced protein-tyrosine phosphatases in adipose tissue.

Insulin resistance in adipose tissue in human obesity is associated with increased protein-tyrosine phosphatase (PTPase) activity and elevated levels of the PTPases leukocyte common antigen-related PTPase (LAR) and PTP1B. To determine whether the improved insulin sensitivity associated with weight loss in obese subjects is accompanied by reversible changes in PTPases, we obtained subcutaneous adipose tissue from seven obese subjects (mean body mass index [BMI], 40.4 kg/m2) before and after a loss of 10% of body weight and again after a 4-week maintenance period. Weight loss was accompanied by an 18.5% decrease in overall adipose tissue PTPase activity (P = .015) that was further reduced to 22.3% of the control value (P = .005) at the end of the maintenance period. By immunoblot analysis, the abundance of LAR was decreased by 21% (P = .04) and abundance of PTP1B was decreased by 40% (P < .004) after the initial weight loss, and the decreases persisted during the maintenance period. Enhanced insulin sensitivity following weight loss, evident from a 26% decrease in fasting insulin levels (P < .05), was also closely correlated with the reduction in the abundance of both LAR (R2 = .80, P < .01) and PTP1B (R2 = .64, P = .03). These results support the hypothesis that LAR and PTP1B may be reversibly involved in the pathogenesis of insulin resistance, and may be therapeutic targets in insulin-resistant states.

Adipocytes↗

PubMed1997

Leptin and the regulation of body weight.

Leptin has received considerable attention as a newly recognized metabolic hormone and for its potential for therapeutic use in the treatment of human obesity. Furthermore, defects in the leptin signal pathway that result in obesity in animal models have raised the possibility of a similar etiology for obesity in humans. This review will summarize the current findings on leptin in both humans and rodents. These findings will be discussed with respect to our view of the physiology and potential for pathophysiology in leptin-mediated regulation of body weight and composition.

Body Weight↗

PubMed1997

Plasma leptin is partly cleared by the kidney and is elevated in hemodialysis patients.

Leptin, the gene product of the ob gene, is important in the control of appetite in rodents and may have an important role in humans. The clearance of leptin from the circulation is unknown. As the leptin receptor is present in the kidney, we evaluated the role of the kidney in removing circulating leptin in humans. We measured leptin in aortic and renal vein plasma in 8 patients with intact renal function and 6 patients with impaired renal function who were undergoing elective cardiac catheterization. Renal blood flow was measured in all patients to calculate net mass balance across the kidney. In patients with intact renal function there is net renal uptake of 12% of circulating leptin, whereas in patients with renal insufficiency there is no renal uptake of leptin. In a separate cohort of 36 patients with end-stage renal failure on hemodialysis, peripheral leptin levels factored for body mass index was increased by > fourfold as compared to a group of healthy controls (N = 338). In addition, plasma leptin is not cleared by hemodialysis with a modified cellulose membrane. Additional studies are required to evaluate the role of leptin in mediating the anorexia of uremia.

Aged↗