Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to growth hormone (GH), sex hormones are important determinants of body composition. Aging is accompanied by a decrease in free testosterone levels and, as BMI as well as fat mass increase with age (with a redistribution of body fat), whereas muscle mass decreases, it is tempting to attribute a causal role to the decrease in androgen levels. In our study involving 372 males aged >20-85, age was found to be positively correlated with BMI and fat mass as measured by impedance, and negatively correlated with levels of free testosterone and free insulin-like growth factor-I. Multiple regression analysis revealed that BMI and age were independent determinants of testosterone levels. The latter decreased from 598+/-188 (SD) ng/dl in the young controls to 453+/-161 ng/dl in the elderly group, free testosterone decreasing from 15.35+/-4.10 to 8.38+/-2.51 ng/dl. Fat-free mass decreased by 18.9%. In a subgroup of 57 men aged 70-80 years, testosterone levels correlated negatively with percentage body fat (r=-0.57), abdominal fat (r=-0.56) and plasma insulin levels (r=-0.40). As GH levels and pulsatility also decrease with age and as, moreover, androgens amplify endogenous secretion of GH, it is not easy to determine the relative role of androgen deficiency in the age-associated changes in body composition. Moreover, increase in fat mass (obesity), as occurs in aging males, is in itself associated with low levels of free testosterone and GH which both normalize after weight reduction. The role of testosterone in the age-associated changes in body composition is, however, further suggested by the increase in lean body mass and in mid-arm circumference and the decrease in waist-to-hip ratio observed after testosterone treatment of elderly men with decreased testosterone levels. Also in healthy eugonadal men, testosterone treatment, at least in supraphysiological doses, causes an important increase in fat-free mass (+/-10%) and in muscle size. The changes in muscle volume are associated with an increase in muscle fibre diameter, suggesting that testosterone induces muscle cell hypertrophy. In conclusion, aging in males is accompanied by an important increase in fat mass and a decrease in lean body mass. Several indices of body composition are significantly correlated with plasma testosterone levels before and after correction for BMI and age. It is evident, however, that in addition to testosterone levels, the age-associated somatopause is also a determinant of the changes in body composition.
 ...
PMID:Testosterone, body composition and aging. 1044 80

Fifty patients with primary GH resistance (Laron syndrome) due to molecular defects of the GH receptor or post-receptor pathways were followed from infancy through adulthood. This condition leading to long-term insulin-like growth factor-I (IGF-I) deprivation caused marked growth retardation (-4 to 8 height SD), acromicia, organomicria, retarded development of the skeletal and muscular systems, a small cranium, slow motor development, and impairment of intellectual development in some of the patients. In addition, there was progressive obesity, insulin resistance, a tendency for hypoglycemia, followed later in life by hypercholesterolemia and by glucose intolerance and even diabetes. IGF-I treatment of children with Laron syndrome, by our and other groups (150-240 microg/day sc), stimulated growth (8 cm in the first year and 4-5 cm in the following years) and normalized the biochemical abnormalities. Overdosage led to adverse effects such as hypoglycemia, edema, swelling of soft tissues, and hyperandrogenism. It is concluded that primary IGF-I deprivation induces severe auxological, biochemical, and hormonal changes, the only treatment being biosynthetic IGF-I administration.
 ...
PMID:The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome. 1059 94

A description of the clinical, biochemical and endocrinological features of the classical form of the syndrome of primary growth hormone (GH) resistance (Laron syndrome) is presented including the progressive changes during follow-up from infancy into adulthood. The main diagnostic features are: severe growth retardation, acromicria, small gonads and genitalia, and obesity. Serum GH levels are elevated and insulin-like growth factor-I (IGF-I) values are low and do not rise upon stimulation by exogenous hGH. The pathogenesis of this syndrome is due to various molecular defects from exon deletion to nonsense, frameshift, splice and missense mutations in the GH receptor (GH-R) gene or in its post-receptor pathways.
 ...
PMID:Natural history of the classical form of primary growth hormone (GH) resistance (Laron syndrome). 1069 88

Leptin circulates in serum bound to high molecular weight proteins. Hypothesizing that leptin binding proteins may regulate the functional efficiency of leptin, we characterized auxologic and hormonal factors that influence leptin binding in three disparate groups: normal adolescents, obese children, and teenagers with type I diabetes mellitus (IDDM). Specific leptin binding activity (sLBA) was assessed by column chromatography after incubation of serum with 125I-leptin in the presence and absence of excess unlabeled leptin. Mean sLBA was 17.0 +/- 7% (SD) in the healthy adolescents (n=41), 6.6 +/-4.3% in the obese children (n=26), and 14.9 +/-7.3% in the diabetic teenagers (n=17). At any value of sLBA, obese children had higher serum leptin levels than non-obese adolescents or diabetic teenagers, consistent with "leptin resistance" in the obese group. sLBA was higher in males than in females only in those with diabetes (18.6 +/- 7.3 vs 10.9 +/- 5.1%, p<0.05). sLBA correlated inversely with serum insulin-like growth factor-I values in the normal group (r= -0.45, p<0.01) and with insulin in the obese children (r= -0.53, p<0.01). There was no correlation between sLBA or serum leptin values and HbA1c, in the diabetic group. The serum leptin concentration was the principal determinant explaining the total variability of sLBA in all three cohorts. However, body mass index (BMI = weight/ height2) accounted for more of the total variability of percent specific binding in the healthy adolescents than in the other groups. We conclude that sLBA reflects circulating leptin levels, body composition, and hormonal milieu. Thus, in addition to leptin, qualitative and quantitative characteristics of leptin binding may play a physiological role in the regulation of appetite and in the "leptin resistance" of obesity.
 ...
PMID:Leptin binding activity (LBA) in plasma of nondiabetic and diabetic adolescents and obese children: relation to auxologic and hormonal data. 1071 58

The possibility that the action of growth hormone (GH) on cartilage is mediated by a separate hormonal agent found in serum was suggested by incubation with hypophysectomized rat costal cartilage. The stability of this tissue permitted long incubations and the measurement of the uptake of 35S-sulfate provided a convenient index of growth stimulation. Under the conditions arbitrarily selected, normal rat serum, but not serum from hypophysectomized rats, induced a great stimulation of 35S uptake. In contrast, GH added directly to cartilage in these incubations was virtually inactive. It was suggested that a serum sulfation factor, now known as insulin-like growth factor-I (IGF-I), was a mediator of GH action. Recently it has been observed that addition of 35S-sulfate after 24 h of preincubation with GH permitted the direct effect of GH to be recognized. Other observations in intact hypophysectomized rats have established that GH can induce the expression of IGF-I in cartilage that acts in an autocrine-paracrine manner. The relative importance of the endocrine and autocrine-paracrine routes of IGF-I action on the growth of cartilage is in dispute. It is clearly established that serum IGF-I exerts a negative feedback on GH secretion by action on the hypothalamus and pituitary. Serum IGF-I concentrations reflect GH action in postnatal life. Measurement of serum IGF-I is the most-valuable index of GH hypersecretion in acromegaly and in conditions of growth impairment. GH receptor deficiency leads to a marked decrease in circulating IGF-I. Hypernutrition and hyperinsulinism of obesity directly promote hepatic IGF-I release and inhibit GH secretion by the pituitary. Differences in hepatic IGF-I synthesis in response to GH may contribute to physiological differences in stature.
 ...
PMID:Growth hormone axis overview--somatomedin hypothesis. 1091 14

The majority of obese persons have hyperinsulinemia and disturbances in the secretion of melatonin, catecholamines and pituitary, thyroid, adrenal and gonadal hormones. These hormones play an important role in the regulation of collagen metabolism either by acting directly or by influencing IGF-I production. This study aimed at ascertaining whether, and to what degree, the changes in the concentration of hormones listed above as well as in the concentration of sex hormone-binding globulin (SHBG) and insulin-like growth factor-I (IGF-I) affect the metabolism of collagen as evaluated indirectly from the measurement of propeptides of type I (PICP) and type III procollagen (PIIINP) in blood serum and hydroxyproline in urine. The study compared 30 women with extreme obesity before and three to five years after jejunoileostomy with 20 healthy women of reproductive age. All non-operated obese women showed significantly increased concentration of serum insulin, IGF-I, melatonin, norepinephrine, free triiodothyronine, estradiol, total and free testosterone, PICP, PIIINP and urinary excretion of hydroxyproline, while the levels of epinephrine, progesterone and SHBG were significantly decreased. Changes in the level of the examined markers of collagen metabolism correlated positively with the concentration of insulin, IGF-I and sex hormones, while the correlation with epinephrine, cortisol and thyroid hormones was negative. All women who were treated previously by jejunoileostomy showed a decreased of body mass to regular values, normalization of hormonal disturbances and normal collagen metabolism. The obtained results show that the increased collagen metabolism observed in extremely obese women is caused indirectly by altered endocrine activity.
 ...
PMID:Assessment of the relationship between collagen metabolism and selected hormonal factors in extremely obese women before and after jejunoileostomy. 1093 49

Prader-Labhart-Willi syndrome (PWS) is the most frequent form of syndromal obesity. Its main features are associated with hypothalamic dysfunction, which has not yet been comprehensively described. The aim of this review is to present arguments to define the presence of genuine growth hormone (GH) deficiency (GHD) in these patients. Decreasing growth velocity despite the onset of obesity, reduced lean body mass in the presence of adiposity, small hands and feet, relatively low insulin-like growth factor-I and low insulin levels, as well as the dramatic effect of GH treatment on growth, support the presence of hypothalamic GHD in PWS. Even though it might be difficult to ultimately prove GHD in PWS because of the obesity-induced counterregulation, the hormonal situation differs from that in simple obesity. The effects of long-term therapies with GH on body composition in these patients are summarized. GH therapy dramatically changes the phenotype of PWS in childhood: height and weight become normal and there is a sustained impact on the net loss of body fat. We conclude that GHD may account for several features of PWS.
 ...
PMID:Is there growth hormone deficiency in prader-willi Syndrome? Six arguments to support the presence of hypothalamic growth hormone deficiency in Prader-Willi syndrome. 1097 Nov 4

Pituitary growth hormone (GH) secretion has been shown to be blunted in human and animal obesity. With respect to human obesity, cafeteria diet-induced obesity might be an appropriate model to study spontaneous GH secretion. In 6 cafeteria diet-overfed obese male Wistar rats and 6 control rats with chronically implanted catheters, GH levels were measured every 15 min over 6 h by standard RIA. A significantly lower GH secretion, reflected by the integrated GH concentration, was found in the obese rats (median 16.46, [range 10.55-19.13] ng/ml x 6 h vs 35.63 [range 21.90-41.50] ng/ml x 6 h, P < 0.05). The GH secretion in the obese rats was significantly negatively correlated with the body fat percentage, assessed by dual X-ray absorptiometry (Rho = -0.95, P < 0.05). Median plasma insulin-like growth factor-I (IGF-I) concentration was comparable between the two groups, while the median insulin concentration was significantly higher in the obese group (1.95 [range 1.76-3.55] ng/ml vs 1.21 [range 0.86-2.13] ng/ml, P < 0.05). No significant correlation existed between GH secretion and the plasma insulin concentration. In conclusion, cafeteria diet-induced obesity is associated with a low spontaneous GH secretion and normal plasma IGF-I concentration. The hyperinsulinemia present in this model probably explains the normal IGF-I concentrations, but not the GH hyposecretion.
 ...
PMID:Cafeteria diet-induced obesity is associated with a low spontaneous growth hormone secretion and normal plasma insulin-like growth factor-I concentrations. 1098 1

Obesity plays a pivotal role in the pathophysiology of metabolic and cardiovascular diseases. Resistance to insulin is commonly seen in metabolic disorders such as obesity and diabetes. Insulin-like growth factor-I (IGF-I) mimics insulin in many tissues and has been shown to enhance cardiac contractile function and growth. Because IGF-I resistance often accompanies resistance to insulin, we sought to determine whether IGF-I-induced myocardial contractile was elevated and whether heart and kidney size were enlarged in obese compared with lean rats. The myocyte contraction profile in the obese rats showed a decreased peak shortening associated with prolonged relengthening and normal shortening duration, a pattern similar to that observed in diabetes. IGF-I (1-500 ng/ml) caused a dose-dependent increase in peak shortening in lean but not obese animals, but it did not alter the duration of shortening and relengthening. Consistent with contractile data, IGF-I induced a dose-dependent increase in Ca(2+) transients only in myocytes of lean rats. IGF-I receptor mRNA levels were significantly reduced in obese rat hearts. These results suggest that the IGF-I-induced cardiac contractile responses are attenuated in the Zucker model of obesity. The mechanisms underlying this alteration may be related to the decreased receptor number and/or changes in intracellular Ca(2+) handling in these animals.
 ...
PMID:Reduced contractile response to insulin and IGF-I in ventricular myocytes from genetically obese Zucker rats. 1100 58

Several recent epidemiological studies have shown an increase in breast cancer risk among women who have elevated plasma levels of testosterone, reduced levels of sex hormone-binding globulin (SHBG), and hence elevated levels of bioavailable androgens and estrogens not bound to SHBG. This endocrine profile is generally associated with obesity and chronic hyperinsulinemia, of which it is most likely a result. Lack of physical activity, obesity, and a diet rich in rapidly digestible carbohydrates and poor in fibre favour the development of insulin resistance and hyperinsulinemia. The elevated insulin levels, in turn are related to decreases in plasma and tissue levels of IGFBP-1 and IGFBP-2 (insulin-like growth factor-binding proteins), and this may increase the availability of insulin-like growth factor-I (IGF-I) to its receptors. Like insulin, IGF-I also inhibits the hepatic synthesis of SHBG, whereas both hormones stimulate the ovarian synthesis of sex steroids. Moreover, insulin and IGF-I can both enhance the development of breast tumours, through their cognate receptors within the mammary tissue. Taken together, these observations lead to the hypothesis that breast cancer risk may be increased in women with elevated plasma insulin levels, and/or with elevated levels of bioactive IGF-I. Hyperinsulinemia and an increased IGF-I bioactivity could thus be an important physiological link between a western lifestyle, overnutrition, a hyperandrogenic sex steroid profile, and increased breast cancer risk. Prospective cohort studies will be needed to test this hypothesis, and to study in greater detail the possible relationships of breast cancer risk with plasma levels of IGF-I and IGFBPs. Confirmation of a relationship of breast cancer risk with plasma insulin levels, on the one hand, or with total plasma IGF-I, on the other hand, could open up new perspectives for breast cancer prevention, either by changes in dietary intake patterns and physical activity, or by the use of certain chemopreventive drugs.
 ...
PMID:[Plasma insulin, IGF-I and breast cancer]. 1130 43


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>