| 1. |
- Carlsson, Björn, 1958, et al.
(författare)
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Obese (ob) gene defects are rare in human obesity
- 1997
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Ingår i: Obesity Research. - 1071-7323 .- 1550-8528. ; 5:1, s. 30-5
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Tidskriftsartikel (refereegranskat)abstract
- Our knowledge of the role of the recently cloned ob-protein (leptin) in the regulation of body fat stores is largely derived from experiments performed in mice. Different mouse models exhibit abnormalities in ob-gene expression, with extreme overexpression in mice which lack bioactive ob-protein, have nonfunctional ob-receptors or hypothalamic lesions, and undetectable expression in mice with suggested defects in regulatory elements. The aim of this study is to examine if defects, corresponding to those in mice, exist in human obesity. Adipose tissue was obtained from 94 adult obese subjects and from six children who had developed obesity after surgery in the hypothalamic region. Total RNA was isolated and ob-gene expression was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot. The coding region of the ob-gene was sequenced in both directions in the 94 obese adults. No mutations were detected in the coding region of the ob-gene and ob-gene expression was detectable in all subjects and none of the subjects had an extreme overexpression. There was no systematic increase in ob-expression in obese children with hypothalamic disease compared to their healthy brothers and sisters. These results show that severe abnormalities involving the ob-gene, analogous to those described in mouse models, are rare in human obesity. We therefore conclude that the cloning and subsequent analysis of the ob-gene has not provided information that can, by itself, explain the genetic component in the development of human obesity.
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| 2. |
- Carlsson, Björn, 1958, et al.
(författare)
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Serum leptin concentrations in relation to pubertal development.
- 1997
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Ingår i: Archives of disease in childhood. - 1468-2044. ; 77:5, s. 396-400
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Tidskriftsartikel (refereegranskat)abstract
- The amount of adipose tissue influences pubertal development and fertility in girls. A candidate for mediating this is the hormone leptin, derived from adipocytes. This work was carried out to determine whether the leptin concentration in serum is regulated during pubertal development.
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| 3. |
- Karlsson, C, et al.
(författare)
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Effects of growth hormone treatment on the leptin system and on energy expenditure in abdominally obese men.
- 1998
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 0804-4643. ; 138:4, s. 408-14
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Tidskriftsartikel (refereegranskat)abstract
- The present study has examined the short- and long-term effects of growth hormone (GH) treatment on the leptin system and energy expenditure. Thirty male individuals with abdominal obesity were randomised to GH or placebo treatment in a 9-month, double-blind study. The dose of GH was 9.5 microg/kg, administered subcutaneously every evening. Serum leptin concentrations were measured by a human leptin RIA. Total RNA was isolated from adipose tissue biopsies and leptin mRNA levels were determined by a semi-quantitative reverse transcriptase-PCR assay. Body composition was determined by potassium-40 and the basal metabolic rate (BMR) was measured by a computerised, ventilated, open-hood system. As compared with placebo, an overall decrease in serum leptin concentrations as assessed by the area under the curve (AUC) (P < 0.05) and an increase in BMR (AUC, P < 0.05) were observed during GH treatment. The overall GH-induced changes were due to marked changes in serum leptin concentrations and BMR after 6 weeks of treatment. After 9 months of GH treatment there was a significant reduction in body fat (BF) while serum leptin concentrations and BMR did not differ from baseline values. Leptin mRNA levels did not change over the study period. We speculate that long-term GH treatment induces a new energy balance steady state with decreased BF stores. The effects of GH on the leptin system is suggested to be of importance for the maintenance of a lower BF mass.
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| 4. |
- Karlsson, C, et al.
(författare)
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Human adipose tissue expresses angiotensinogen and enzymes required for its conversion to angiotensin II.
- 1998
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 83:11, s. 3925-9
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Tidskriftsartikel (refereegranskat)abstract
- Angiotensin II regulates blood pressure and may affect adipogenesis and adipocyte metabolism. Angiotensin II is produced by cleavage of angiotensinogen by renin and angiotensin-converting enzyme in the circulation. In addition, angiotensin II may be produced in various tissues by enzymes of the renin-angiotensin system (RAS) or the nonrenin-angiotensin system (NRAS). We have analyzed the expression of angiotensinogen and enzymes required for its conversion to angiotensin II in human adipose tissue. Northern blot demonstrated angiotensinogen expression in adipose tissue from nine obese subjects. Western blot revealed a distinct band of expected size of the angiotensinogen protein (61 kDa) in isolated adipocytes. RT-PCR, followed by Southern blot, demonstrated renin expression in human adipose tissue. Angiotensin-converting enzyme messenger RNA was detected by RT-PCR, and the identity of the PCR products was verified by restriction enzyme cleavage. Transcripts for cathepsin D and cathepsin G, components of the NRAS, were detected by RT-PCR, verified by restriction enzyme cleavage. We conclude that human adipose tissue expresses angiotensinogen and enzymes of RAS and NRAS. This opens the possibility that angiotensinogen-derived peptides, produced in adipose tissue itself, may affect adipogenesis and play a role in the pathogenesis of obesity.
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| 5. |
- Lindroos, Anna-Karin, 1958, et al.
(författare)
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Familial predisposition for obesity may modify the predictive value of serum leptin concentrations for long-term weight change in obese women
- 1998
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Ingår i: American Journal of Clinical Nutrition. ; 67, s. 1119-1123
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Tidskriftsartikel (refereegranskat)abstract
- Department of Internal Medicine and the Research Centre for Endocrinology and Metabolism, Sahlgrenska University Hospital, Göteborg, Sweden. Leptin is believed to play a role in regulating food intake and body weight. The aim of this study was to examine the influence of parental history of obesity on the association between baseline serum leptin concentrations and subsequent 4-y weight changes. Changes in food intake were also considered in the analysis. Middle-aged, obese women with no obese parent (n = 25) or at least one obese parent (n = 24) were included in the analysis. At baseline, women with no parental history of obesity and women with a parental history of obesity did not differ in body mass index (in kg/m2: 41.2 and 40.2, respectively) or median leptin concentrations (40.8 and 38.8 microg/L, respectively). Four-year weight changes varied widely in both groups combined (from -30 to 24 kg). Stratified regression analysis, adjusted for age, weight, and height, revealed that high leptin concentrations predicted less weight gain (or more weight loss) in women with no obese parent (beta = -21.2, P = 0.0006) but played no significant role in predicting weight gain in women with at least one obese parent (beta = -3.8, P = 0.41). Adding changes in energy and fat intakes to the model reduced the association between leptin and weight change to nonsignificance in the women with no obese parent, indicating that the effect of leptin could be explained largely by dietary changes. In conclusion, serum leptin concentrations predict long-term weight change in obese women with no history of parental obesity, an association largely mediated by changes in food intake. PMID: 9625082 [PubMed - indexed for MEDLINE]
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| 6. |
- Lindroos, Anna-Karin, 1958, et al.
(författare)
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Familial predisposition for obesity may modify the predictive value of serum leptin concentrations for long-term weight change in obese women.
- 1998
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Ingår i: The American journal of clinical nutrition. - 0002-9165. ; 67:6, s. 1119-23
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Tidskriftsartikel (refereegranskat)abstract
- Leptin is believed to play a role in regulating food intake and body weight. The aim of this study was to examine the influence of parental history of obesity on the association between baseline serum leptin concentrations and subsequent 4-y weight changes. Changes in food intake were also considered in the analysis. Middle-aged, obese women with no obese parent (n = 25) or at least one obese parent (n = 24) were included in the analysis. At baseline, women with no parental history of obesity and women with a parental history of obesity did not differ in body mass index (in kg/m2: 41.2 and 40.2, respectively) or median leptin concentrations (40.8 and 38.8 microg/L, respectively). Four-year weight changes varied widely in both groups combined (from -30 to 24 kg). Stratified regression analysis, adjusted for age, weight, and height, revealed that high leptin concentrations predicted less weight gain (or more weight loss) in women with no obese parent (beta = -21.2, P = 0.0006) but played no significant role in predicting weight gain in women with at least one obese parent (beta = -3.8, P = 0.41). Adding changes in energy and fat intakes to the model reduced the association between leptin and weight change to nonsignificance in the women with no obese parent, indicating that the effect of leptin could be explained largely by dietary changes. In conclusion, serum leptin concentrations predict long-term weight change in obese women with no history of parental obesity, an association largely mediated by changes in food intake.
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| 7. |
- Lissner, Lauren, 1956, et al.
(författare)
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Birth weight, adulthood BMI, and subsequent weight gain in relation to leptin levels in Swedish women
- 1999
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Ingår i: Obesity Research. ; 7, s. 150-154
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Tidskriftsartikel (refereegranskat)abstract
- Department of Internal Medicine, Göteborg University, Sweden. Lauren.Lissner@medfak.gu.se OBJECTIVE: Leptin seems to be involved in the regulation of energy balance, although little is known about the epidemiology of leptin with respect to prediction of weight gain and incidence of obesity-related diseases. The dual aim of this study is to document characteristics of leptin after long-term storage, and to describe its relation to body weight, from birth to old age, in an ongoing prospective study. RESEARCH METHODS AND PROCEDURES: A population-based sample of Swedish women was first examined at the ages of 38 to 60 and re-examined 24 years later. This study used 1358 frozen serum samples that had been stored 29 years for analysis of leptin concentrations and their relation to body weight history. RESULTS: Leptin values obtained from stored samples showed the same correlation with relative weight as that seen in a contemporary sample with similar demographic characteristics. Lower self-reported birth weight was associated with higher leptin levels in adulthood (p = 0.01), controlling for age and adult BMI. Prospective analyses revealed that high leptin in 38 to 46-year-olds predicted subsequent long-term weight gain (p = 0.003), although no significant associations were seen in women initially aged 50 or older. DISCUSSION: It is feasible to use frozen serum for studying leptin in relation to obesity and related developments many years later. High leptin level was a risk factor for subsequent weight gain in 38- and 46-year-old women. Retrospective analyses involving birth weight suggest that leptin resistance in adulthood might have fetal origins. PMID: 10102251 [PubMed - indexed for MEDLINE]
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| 8. |
- Torgerson, Jarl S, 1960, et al.
(författare)
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A low serum leptin level at baseline and a large early decline in leptin predict a large 1-year weight reduction in energy-restricted obese humans.
- 1999
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 84:11, s. 4197-203
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Tidskriftsartikel (refereegranskat)abstract
- The difficulty in maintaining weight loss during obesity treatment may be caused by a counteracting neuroendocrine response. It has been proposed that leptin could be a regulator of this response. We examined the relations between leptin levels during an initial very low calorie diet, other simultaneous endocrine changes, and the 1-yr weight reduction. Sixty-nine obese (24 men and 45 women) were treated with very low calorie diet for 16 weeks, followed by a hypocaloric diet for 32 weeks. Serum levels of leptin, insulin, cortisol, and thyroid hormones were measured at weeks 0, 8, and 18. The relative weight reductions after 18 and 48 weeks were 20.1% and 14.4% in men and 15.4% and 11.8% in women. Low initial leptin levels and large declines in serum leptin were associated with a large 1-yr weight loss in both genders. Leptin levels (baseline or changes) were not independently associated with the changes in insulin, cortisol, or thyroid hormones. Our results may indicate that leptin by itself could be of minor importance for the neuroendocrine response to severe caloric restriction in humans.
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| 9. |
- Wickelgren, Ruth, 1965, et al.
(författare)
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Expression of exon 3-retaining and exon 3-excluding isoforms of the human growth hormone-receptor is regulated in an interindividual, rather than a tissue-specific, manner.
- 1995
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Ingår i: The Journal of clinical endocrinology and metabolism. - 0021-972X. ; 80:7, s. 2154-7
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Tidskriftsartikel (refereegranskat)abstract
- GH has multiple effects on growth and metabolism, and these functions are mediated through binding to specific cell surface receptors. The human GH receptor (GHR) exists in two known isoforms; in one form exon 3 is present (GHR3+), and in the other, exon 3 is absent (GHR3-). Recent reports have suggested that the expression of the two isoforms is tissue specific and/or developmentally regulated. We used a reverse transcription-polymerase chain reaction assay to study the expression pattern of the two isoforms in a variety of tissues from normal subjects and patients with acromegaly. In skeletal muscle from both normal subjects and patients with acromegaly, the GHR3+ transcript was expressed, either alone or together with the shorter (GHR3-) transcript. When multiple tissues from six subjects were tested, the expression of the two isoforms varied among subjects, whereas different tissues from the same subject showed the same expression pattern. These results indicate that the expression of the GHR isoforms is not tissue specific. Instead, the expression of the GHR isoforms appears to be specific for each individual, suggesting that it is under the control of factors that affect all tissues in the body.
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