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K M Pirke

Publications and source records attributed to K M Pirke.

At least 19 recordsLinked to original sources
PubMed2004

[Basal metabolic rate and energy expenditure in the elderly].

The purpose of this study was to investigate energy requirements in healthy elderly subjects. Total daily energy expenditure (TEE) and resting metabolic rate (RMR) were measured by the doubly labeled water technique and indirect calorimetry in 36 healthy free living elderly men and women. Over a 15 day period additional measurements were made of dietary intake, physical activity and body composition. TEE did not differ between women and men (2941+/-439 vs 2965+/-543 kcal/d; p=ns), ranging from 2124 to 3968 kcal/d. Resting metabolic rate was significantly lower in women compared to men (1345+/-194 vs 1543+/-303 kcal/d; p=0.016). The TEE data were compared to the food diaries. Women and men underestimated their food intake significantly. TEE varies greatly within elderly subjects due to the variation in body weight and physical activity.

Activities of Daily Living↗
PubMed2004

Allostatic load, perceived stress, and health: a prospective study in two age groups.

Overactivity of the hypothalamus-pituitary-adrenal axis (HPAA) has been observed in the presence of acute stress and, under chronic conditions, in disorders such as depression and anorexia nervosa as well as in cardiovascular and metabolic disorders. However, there may be other stress-related disorders (fatigue, pain, etc) that seem to be associated with mild hypocortisolism. This suggests that two major subtypes of the HPAA response to stress need to be discriminated. In this study, we investigated 76 subjects with and without hypocortisolism, respectively, over a 1-year period. Surprisingly, hypocortisolemic subjects had a lower allostatic load but they scored higher on measures of depression, perceived stress, and physical complaints. We propose a protective role of the hypocortisolemic stress response on cardiovascular and metabolic disorders, particularly in the elderly.

Adult↗
PubMed2000

Functional characterization of the 5'-flanking and the promoter region of the human UCP3 (hUCP3) gene.

Uncoupling protein-3 (UCP3) is considered as an important regulator of energy expenditure and thermogenesis in humans. To get insight into the mechanisms regulating its expression we have cloned and characterized about 5 kb of the 5'-flanking region of the human UCP3 (hUCP3) gene. 5'-RACE analysis suggested a single transcription initiation site 187 bp upstream from the translational start site. The promoter region contains both TATA and CAAT boxes as well as consensus motifs for PPRE, TRE, CRE and muscle-specific factors like MyoD and MEF2 sites. Functional characterization of a 3 kb hUCP3 promoter fragment in multiple cell lines using a CAT-ELISA identified a cis-acting negative regulatory element between -2983 and -982 while the region between -982 and -284 showed greatly increased basal promoter activity suggesting the presence of a strong enhancer element. Promoter activity was particularly enhanced in the murine skeletal muscle cell line C2C12 reflecting the tissue-selective expression pattern of UCP3.

5' Untranslated Regions↗
PubMed1999

Molecular cloning and functional characterization of the promoter region of the human uncoupling protein-2 gene.

As a member of the uncoupling protein family, UCP2 is ubiquitously expressed in rodents and humans, implicating a major role in thermogenesis. To analyze promoter function and regulatory motifs involved in the transcriptional regulation of UCP2 gene expression, 3.3 kb of 5'-flanking region of the human UCP2 (hUCP2) gene have been cloned. Sequence analysis showed that the promoter region of hUCP2 lacks a classical TATA or CAAT box, however, appeared GC-rich resulting in the presence of several Sp-1 motifs and Ap-1/-2 binding sites near the transcription initiation site. Functional characterization of human UCP2 promoter-CAT fusion constructs in transient expression assays showed that minimal promoter activity was observed within 65 bp upstream of the transcriptional start site (+1). 75 bp further upstream (from nt -141 to -66) a strong cis-acting regulatory element (or enhancer) was identified, which significantly enhanced basal promoter activity. The regulation of human UCP2 gene expression involves complex interactions among positive and negative regulatory elements distributed over a minimum of 3.3 kb of the promoter region.

Animals↗
PubMed1999

Structural organization and mutational analysis of the human uncoupling protein-2 (hUCP2) gene.

Uncoupling proteins (UCPs) are mitochondrial membrane transporters which are involved in dissipating the proton electrochemical gradient thereby releasing stored energy as heat. This implies a major role of UCPs in energy metabolism and thermogenesis which when deregulated are key risk factors for the development of obesity and other eating disorders. From the three different human UCPs identified so far by gene cloning both UCP2 and UCP3 were mapped in close proximity (75-150 kb) to regions of human chromosome 11 (11q13) that have been linked to obesity and hyperinsulinaemia. At the amino acid level hUCP2 has about 55% identity to hUCP1 while hUCP3 is 71% identical to hUCP2. In this study we have deduced the genomic structure of the human UCP2 gene by PCR and direct sequence analysis. The hUCP2 gene spans over 8.7 kb distributed on 8 exons. The localization of the exon/intron boundaries within the coding region matches precisely that of the hUCP1 gene and is almost conserved in the recently discovered hUCP3 gene as well. The high degree of homology at the nucleotide level and the conservation of the exon /intron boundaries among the three UCP genes suggests that they may have evolved from a common ancestor or are the result from gene duplication events. Mutational analysis of the hUCP2 gene in a cohort of 172 children (aged 7 - 13) of Caucasian origin revealed a polymorphism in exon 4 (C to T transition at position 164 of the cDNA resulting in the substitution of an alanine by a valine at codon 55) and an insertion polymorphism in exon 8. The insertion polymorphism consists of a 45 bp repeat located 150 bp downstream of the stop codon in the 3'-UTR. The allele frequencies were 0.63 and 0.37 for the alanine and valine encoded alleles, respectively, and 0.71 versus 0.29 for the insertion polymorphism. The allele frequencies of both polymorphisms were not significantly elevated in a subgroup of 25 children characterized by low Resting Metabolic Rates (RMR). So far a direct correlation of the observed genotype with (RMR) and Body Mass Index (BMI) was not evident. Expression studies of the wild type and mutant forms of UCP2 should clarify the functional consequences these polymorphisms may have on energy metabolism and body weight regulation.

3' Untranslated Regions↗
PubMed1999

Reduced resting metabolic rate in athletes with menstrual disorders.

PURPOSE: This study investigated metabolic and nutritional determinants in association with menstrual disorders in athletes. Athletes with normal menstrual function (AN; N = 21) and athletes with menstrual disorders (AD: N = 12) participated in this study. METHODS: The quality of the menstrual cycle was judged according to salivary progesterone concentrations. Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) were measured by indirect calorimetry. Body composition, energy intake and restrained eating scores were obtained. RESULTS: When adjusted for body composition by ANCOVA, RMR was significantly (approximately 460 kJ, P < 0.02) lower in athletes with menstrual disorders than in athletes without menstrual disorders. The DIT and the daily energy intake of the groups did not differ. Athletes with menstrual disturbances scored significantly higher on the Restraint Eating Scale (TFEQ). Thyroid hormones (fT3 and fT4), analyzed by a competitive chemiluminescent immunoassay, were in the normal range and not different between groups. CONCLUSIONS: The results provide evidence that restrained eating and low RMR are associated with menstrual cycle disturbances in athletes.

Adult↗
PubMed1998

Resting metabolic rate in preadolescent girls at high risk of obesity.

OBJECTIVE: To investigate whether children at high risk of obesity have a reduced resting metabolic rate (RMR). DESIGN: Cross-sectional study. SUBJECTS: 93 healthy girls (age: 8-12 y) were allocated to one of four groups, according to the subjects' and their parents' weight status: group 1, overweight children with both parents overweight (OB/OB2; n = 17); group 2, normal weight children with both parents overweight (N/OB2; n = 28); group 3, overweight children of discordant parents (OB/OB1; n = 21) and group 4, normal weight children with both parents normal weight (N/OB0; n = 27). MEASUREMENTS: Weight, height, fat-free mass (FFM) and fat mass (FM) by bioelectrical impedance analysis (BIA), RMR (indirect calorimetry) for the duration of 25 min. RESULTS: Controlling for disparities in body composition, age and physical maturity, significant differences were found in adjusted group means of RMR (OB/OB2 1181 kcal/d; N/OB2 1276 kcal/d; OB/OB1 1234 kcal/d; N/OB0 1199 kcal/d; P < 0.02) with the OB/OB2 girls showing the lowest energy expenditure. CONCLUSION: We found evidence that preadolescent girls at risk of obesity, are not generally predisposed to a higher body weight, because of a greater metabolic efficiency. In fact, our data show that more emphasis should be laid on defining different subgroups of both overweight and normal weight subjects in studies investigating metabolic rate.

Aging↗
PubMed1998

Sex differences in endocrine and psychological responses to psychosocial stress in healthy elderly subjects and the impact of a 2-week dehydroepiandrosterone treatment.

Evidence from animal as well as human studies has suggested that significant sex differences exist in hypothalamus-pituitary-adrenal axis (HPA) activity. As gonadal steroids could be important modulators of HPA sex differences, stress responses were investigated in subjects of advanced age after dehydroepiandrosterone (DHEA) or placebo treatment. After a 2-week treatment with 50 mg DHEA daily or placebo, 75 men and women (mean age, 67.6 yr) were exposed to the Trier Social Stress Test (TSST). The TSST is a brief psychosocial stress that consists of a free speech and mental arithmetic task in front of an audience. The results show that the TSST induced significant increases in ACTH, salivary free cortisol, total plasma cortisol, norepinephrine, and heart rates (all P < 0.0001) as well as decreased positive affect in the elderly (P = 0.0009). Men showed larger stress responses in ACTH (P = 0.004), salivary free cortisol (P = 0.044), and plasma total cortisol (P = 0.076) compared to women. No sex differences were observed in norepinephrine, epinephrine, or heart rate responses. In contrast to ACTH and cortisol response differences, women reported that they were significantly more stressed by the TSST than men (P = 0.0051). Women treated with DHEA showed ACTH stress responses similar to those of men, but significantly enhanced compared to those of women taking placebos (P < 0.009). No other stress response differences emerged between DHEA and placebo groups. Finally, DHEA treatment did not result in an improvement of subjective well-being. We conclude that elderly men show larger HPA responses than women to psychosocial stress, as studied in the TSST. Estrogen effects on hypothalamic CRF-producing neurons might be responsible for these sex differences.

Adrenocorticotropic Hormone↗
PubMed1998

[Psychosomatic aspects of obesity].

Obesity is characterised by an imbalance of caloric intake and energy expenditure. Increased caloric uptake and reduced physical activity are important. No specific psychopathology exists in obesity. Obese people view their body weight and form significantly more negative than lean controls and often experience depression and anxiety. Quality of life is often impaired. Obesity causes many disadvantages in interpersonal and social aspects. 30% of the obese subjects report binge eating. Whether binge eating should be considered as an independent syndrome is currently under discussion. The treatment of obesity is not satisfactory. Pharmacological approaches have so far failed. Behavioral therapy including dieting of different forms is not successful in long terms. 95% of the patients regain body weight within five years. Surgical therapy are very successful but should be only applied in severe obesity.

Body Image↗
PubMed1997

Evaluation of a Cys23Ser mutation within the human 5-HT2C receptor gene: no evidence for an association of the mutant allele with obesity or underweight in children, adolescents and young adults.

Serotonin is a neurotransmitter involved in a large number of psychophysiological processes including the regulation of mood, arousal, aggression, sleep, learning, nociceptions, nerve growth and importantly, appetitive functions. Alterations of 5-HT receptor activity have been shown to occur in many psychiatric diseases including depression, anxiety, eating disorders, schizophrenia etc. Hence, genetic variation in genes coding for serotonin receptor proteins might well be involved in the genetic predisposition to these diseases and therefore are of great pharmacogenetic relevance. Knockout mice deficient of a functional 5-HT2C receptor have implicated a potential role of this receptor subtype in the serotonergic control of appetite. A Cys23Ser mutation in the human 5-HT2C receptor gene discovered recently prompted us to investigate this mutation with regard to the development of human obesity. We have evaluated this mutation in 241 obese children and adolescents (mean BMI > or = 97th percentile), 80 normal weight children (BMI 5th-85th percentile) and 92 underweight probands (BMI < or = 15th percentile) for a possible association with obesity. The frequencies of the mutant allele in all three weight groups (obese subjects: 0.1597; normal weight: 0.168; underweight: 0.1575) were very similar. Association as well as linkage studies were negative. Therefore it is unlikely that this receptor mutation plays a direct role in the development of human obesity.

Adolescent↗
PubMed1997

Serotonin transporter gene-linked polymorphic region: allele distributions in relationship to body weight and in anorexia nervosa.

Several lines of evidence implicate a role for the serotonergic system in body weight regulation and eating disorders. The magnitude and duration of postsynaptic responses to serotonin (5-HT) is directed by the transport into and release from the presynaptic neuron. Recently, a common polymorphism of a repetitive element in the region of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) was identified that results in a system of two common alleles. The activity of the 5-HTT, as measured in in vitro assays and in human lymphoblastoid cell lines, is dependent on the respective genotype. We thus hypothesized that this polymorphism is relevant for weight regulation in general and is possibly involved in the etiology of anorexia nervosa (AN). Allele frequencies and genotypes were determined in a total of 385 unrelated obese children, adolescents and adults, 112 underweight subjects and 96 patients with AN. Furthermore, both parents of 98 obese children and adolescents and of 55 patients with AN, respectively, were genotyped, thus allowing to test for both association and linkage. The comparison of allele frequencies between obese and underweight probands provided no evidence for a major role of the 5-HTTLPR in weight regulation. Patients with AN had allele frequencies not significantly different to those observed for obese and underweight individuals.

Adolescent↗
PubMed1997

A comparison of resting metabolic rate, self-rated food intake, growth hormone, and insulin levels in obese and nonobese preadolescents.

The objective was to investigate metabolic (resting metabolic rate), behavioral (energy intake), and endocrine variables (fasting insulin and growth hormone levels) potentially responsible for a positive energy balance in obese children in a cross-sectional study. The study was in 25 obese children aged 8 to 12 years and 21 nonobese children of the same age range. Weight, height, lean body mass (LBM) and fatmass (FM) were measured by bioelectrical impedance analysis, resting metabolic rate (indirect calorimetry) for the duration of 25 min, 7-day food records and fasting levels of insulin and human growth hormone (HGH). In the total sample, no differences were found in resting metabolic rate (RMR controlled for differences in weight) and energy intake between groups, whereas fasting insulin level was significantly higher and basal growth hormone concentration was significantly lower in the obese children. In RMR, there were significant age-dependent differences only in 10-year-old children, with the obese subjects showing lower values. The results fit in a multidimensional model, taking into account a critical period in prepubertal age for the development of childhood obesity. This period may be characterized by a reduced RMR, which results in an increased body weight, even if there is no excessive energy intake.

Body Composition↗
PubMed1997

Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa.

OBJECTIVE: The missense mutation (64Trp to 64Arg) in the beta 3-adrenergic-receptor has previously been described to confer a genetic predisposition to the development of obesity. DESIGN: To test the hypothesis we evaluated allele frequencies in children, adolescents and young adults who belonged to different weight groups that were delineated with percentiles for the body mass index (BMI; kg/m2). SUBJECTS: 99 underweight probands (BMI < or = 15th percentile). 80 normal weight probands (BMI: 5th-85th percentile). 238 obese children and adolescents (BMI > or = 97th percentile). 84 patients with anorexia nervosa (AN). MEASUREMENTS: The cohorts were screened by polymerase chain reaction with subsequent restriction fragment length polymorphism (PCR-RFLP) analysis. Data were statistically analysed for association. In addition to these case control studies, the transmission disequilibrium test (TDT) was applied to 80 families of obese probands and to 52 families of patients with AN. RESULTS: Both the tests for association and linkage were negative. The Trp64Arg allele frequencies in the three weight groups (obesity: 0.071; normal weight: 0.081; underweight: 0.056) and the AN patients (0.054) were similar. Extremely obese individuals showed no excess of the Trp64Arg allele. No homozygotes for the Trp64Arg allele were detected. CONCLUSION: Heterozygosity for the Trp64Arg allele is not of major importance in regulation of body weight in individuals younger than 35 y. Additionally, the extreme obese subgroup is not enriched for the polymorphism.

Adolescent↗
PubMed1997

Episodic variations of prolactin, thyroid-stimulating hormone, luteinizing hormone, melatonin and cortisol in infertile women with subclinical hypothyroidism.

Preliminary data have suggested that female infertility due to corpus luteum insufficiency may be caused by subclinical hypothyroidism [exaggerated thyroid-stimulating hormone (TSH) response to thyrotrophin-releasing hormone (TRH) stimulation]. L-Thyroxine supplementation has been recommended to achieve pregnancies in subclinical hypothyroid women. This controlled study was carried out in order to investigate the biochemical diagnosis of subclinical hypothyroidism as a possible infertility factor. Five infertile patients (aged 25-36 years) with subclinical hypothyroidism (n = 4, stimulated TSH >20 microU/ml) or primary hypothyroidism (n = 1) and five healthy controls (aged 22-39 years) with normal thyroid function (stimulated TSH <15 microU/ml), regular cycles and no history of infertility were studied in the early follicular phase. In the pre-study evaluation, eight of 23 volunteers (34.8%) had to be excluded because of subclinical hypothyroidism with stimulated TSH values (TSHs) >15 microU/ml. Cycle function of patients and controls was compared by the method of LH pulse pattern analysis. Therefore blood samples were drawn every 10 min during a 24 h period. Sleep was recorded from midnight to 7 a.m. Repetition of the TRH tests at the end of the 24 h blood sampling period confirmed the difference in stimulated TSH values of the two study groups. Pulse analysis for luteinizing hormone (LH), TSH and prolactin showed no differences between patients and controls for pulse frequency, amplitude, height, length, area under curve (AUC) and the 24 h mean. Even the hypothyroid patient had a normal LH pulse pattern. Additional measurement of melatonin in pooled sera every 30 min gave the well-documented diurnal profiles during day and night for both groups. Patients had significantly higher melatonin values at seven time points during the night. Peaks for LH, TSH, prolactin and cortisol were correlated with the sleep stages wake, rapid eye movement, 1 + 2 and 3 + 4. We concluded that corpus luteum insufficiency in female infertility cannot be explained by subclinical hypothyroidism and thus should not be treated with L-thyroxine for fertility reasons.

Adult↗
PubMed1997

Effects of fasting and glucose load on free cortisol responses to stress and nicotine.

The availability of energy appears to exert important regulatory functions in pituitary-adrenal stress responses. In two studies, the effects of short-term fasting and subsequent glucose administration on the free cortisol response to psychological stress and nicotine consumption were investigated. Study 1: After fasting for 8-11 h, healthy young men ingested either 100 g glucose (n = 13) or water (n = 12). One hour later they were exposed to a psychosocial stress task (Trier Social Stress Test). A third group also ingested 100 g glucose, but they were not exposed to any additional treatment (n = 10). Capillary blood glucose levels were in the lower euglycemic range before and significantly elevated after the glucose load (64.9 +/- 9.8 vs. 162.5 +/- 43.5 mg/dL; F = 149.04, P < 0.001). Although glucose load per se did not affect free cortisol levels, psychosocial stress induced a large cortisol response in glucose-treated subjects. In contrast, fasted subjects who received tap water did not respond to the Trier Social Stress Test with significant changes in cortisol levels (F = 6.27, P < 0.001). Both groups responded with a similar increase in heart rates (F = 33.53, P < 0.001) with no statistically significant difference between glucose and water-treated subjects. Study 2: Twelve habitual smokers received 100 g glucose or tap water after fasting for at least 8 h on two separate sessions (cross-over, random sequence). Forty-five min after glucose/water ingestion, they smoked two cigarettes with a nicotine content of 1.0 mg/cigarette. Subjects were euglycemic before smoking, with a significant rise of glucose levels after consumption of 100 g glucose (64.4 +/- 8.3 vs. 143.5 +/- 40.0 mg/dL; F = 40.25, P < 0.001). As in Exp 1, subjects showed a substantially larger free cortisol response to nicotine under glucose load compared with water load (F = 4.91, P < 0.001). From these data we conclude that the free cortisol response to stimulation is under significant control of center responsible for monitoring energy availability. Low glucose levels appear to inhibit adrenocortical responsiveness in healthy subjects. In agreement with results from animal studies, the present results suggest that ready access to energy is a prerequisite for hypothalamus-pituitary-adrenal stress responses.

Adult↗
PubMed1997

Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men.

The levels of dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS decrease with age after a peak around 25 yr. Animal studies as well as the first studies in humans have generated the idea that DHEA replacement in elderly subjects may have beneficial effects on well-being and cognitive functions. In the present experiment 40 healthy elderly men and women (mean age, 69 yr) participated in a double blind, placebo-controlled DHEA substitution study. For 2 weeks subjects took 50 mg DHEA daily, followed by a 2-week wash-out period and a 2-week placebo period. The treatment sequence was randomized in a cross-over design. After 2 weeks of DHEA or placebo, psychological and physical well-being as well as cognitive performance were assessed using several questionnaires and neuropsychological tests. All subjects had low DHEAS baseline levels. DHEA substitution lead to a 5-fold increase in DHEAS levels in women (from 0.67 +/- 0.1 to 4.1 +/- 0.4 micrograms/mL; P < 0.001) and men (from 0.85 +/- 0.1 to 4.5 +/- 0.4 micrograms/mL; P < 0.001). DHEA, androstenedione, and testosterone levels also increased significantly in both sexes (all P < 0.001). No significant changes were observed in insulin-like growth factor I or insulin-like growth factor-binding protein-3 levels. DHEA replacement had no strong beneficial effect on any of the measured psychological or cognitive parameters. Only women tended to report an increase in well-being (P = 0.11) and mood (P = 0.10), as assessed with questionnaires. They also showed better performance in one of six cognitive tests (picture memory) after DHEA. However, after Bonferroni alpha adjustment, this difference was no longer significant. No such trend was observed in men (P > 0.20). Likewise, no beneficial effects of DHEA substitution could be observed in any of the other tests of the neuropsychological test battery in either sex (all P > 0.20). In conclusion, the present data do not support the idea of strong beneficial effects of a physiological DHEA substitution on well-being or cognitive performance in healthy elderly individuals.

Affect↗
PubMed1996

Central and peripheral noradrenalin regulation in eating disorders.

Norepinephrine and its metabolites were studied in various body fluids (plasma, urine and cerebrospinal fluid) of patients with anorexia nervosa, bulimia nervosa and healthy young women. The reaction of plasma norepinephrine to different stimuli like orthostatic challenge, test meals, standardized exercise, mental challenge tests etc. were studied. All results indicate a reduced noradrenergic activity in the central and peripheral nervous system of patients with eating disorders. The clinical consequences of these changes are hypotension, bradicardia, hypothermia and depression. Evidence is presented that the reduced activity of the sympathetic nervous system is caused by starvation (anorexia nervosa) or intermittent dieting (bulimia nervosa).

Anorexia Nervosa↗