Stress-induced cortisol, mood, and fat distribution in men.

OBJECTIVE: A previous study in our laboratory (Moyer et al., Obes Res. 1994;2:255-62 found that, in response to uncontrollable laboratory stress, women with a high waist-to-hip ratio (WHR) had higher cortisol reactivity, poorer coping skills, and lower anger responses than women with low WHR. We aimed to compare high WHR men's stress responses to these women. RESEARCH METHODS AND PROCEDURES: The current study examined cortisol reactivity and psychological data of 27 healthy high WHR men exposed to the same laboratory challenges as the women from our previous study. Men's data are discussed in relation to that of the high and low WHR women. RESULTS: Men responded to the stress with increases in both cortisol and blood pressure. In comparison with the high and low WHR women, men had significantly higher total cortisol on the stress day. However, when comparing a sub-sample of men and women matched in WHR's, differences in cortisol secretion were greatly diminished and no longer significant. In addition, men had higher desire for control than both high and low WHR women, and lower mood reactivity than low WHR women. Despite the lower mood reactivity of high WHR groups, the high mood reactors among the high WHR women, and to a lesser extent, men, tended to have higher cortisol reactivity. DISCUSSION: These results suggest that the psychological differences and greater exposure to cortisol observed among the high WHR men and women may have played a role in contributing to their greater abdominal fat depots.

Differential effects of fat and sucrose on the development of obesity and diabetes in C57BL/6J and A/J mice.

We have previously demonstrated that the C57BL/6J (B/6J) mouse will develop severe obesity, hyperglycemia, and hyperinsulinemia if weaned onto a high-fat, high-sucrose (HH) diet. In the present study, we compared the effects of fat and sucrose separately and in combination on diabetes- and obesity-prone B/6J and diabetes- and obesity-resistant A/J mice. After 4 months, the feed efficiency ([FE] weight gained divided by calories consumed) did not differ across diets in A/J mice, but B/6J mice showed a significantly increased FE for fat. That is, B/6J mice gained more weight on high-fat diets without consuming more calories than A/J mice. The increase in FE was related to adipocyte hyperplasia in B/6J mice on high-fat diets. Fat-induced obesity in B/6J mice was unrelated to adrenal cortical activity. In the absence of fat, sucrose produced a decreased in FE in both strains. Animals fed a low-fat, high-sucrose (LH) diet were actually leaner than animals fed a high-complex-carbohydrate diet. Fat was also found to be the critical stimulus for hyperglycemia and hyperinsulinemia in B/6J mice. In the absence of fat, sucrose had no effect on plasma glucose or insulin. These data clearly show that across these two strains of mice, genetic differences in the metabolic response to fat are more important in the development of obesity and diabetes than the increased caloric content of a high-fat diet.

Effect of dexfenfluramine on fat mass distribution in a high-fat rat model.

It has been shown that in contrast to peripheral fat, visceral fat is an important risk factor for cardiovascular diseases and diabetes. In this study, we investigated whether dexfenfluramine (dF), a compound known to decrease body fat, affects fat mass differentially in various regions of the body. We used a moderately obese rat model fed a high-fat diet (40% fat). After 35 days on the diet, rats were divided into three groups: a dF-treated group ([D]2.5 mg/kg intraperitoneally twice daily), a pair-fed group (Cp), and a control group (C) fed ad libitum. C and Cp rats were injected with saline. After 4 weeks of treatment, body fat, fat cell morphology, and metabolism were determined in subcutaneous (inguinal [ING]) and visceral (retroperitoneal [RET] and mesenteric [MES]) fat tissues. Food intake in D and Cp rats was similar, and was lower than in the C group. In comparison to Cp and C rats, D rats had lower body weight and body fat, smaller ING and RET fat pad weights, and smaller fat cell size in all depots. No significant differences were observed in fat mobilization between groups; however, fat accumulation tended to be lower in D rats. These data suggest that dF has an effect on adipose tissue independent of its effect on food intake. However, this effect seems to occur without regional specificity.

Stress-induced cortisol response and fat distribution in women.

Recent studies have shown an association between uncontrollable stress and abdominal fat distribution. It has been suggested that changes in cortisol secretion might represent one possible mechanism for this relationship. This study investigated whether body fat distribution, determined by waist-to-hip ratio (WHR), is related to salivary cortisol levels in response to laboratory stressors. Subjects were 41 overweight women with a Low or a High WHR. Multiple measures of cortisol and mood were obtained during a session of stressful tasks (eg., timed arithmetic) and during a time-matched, control rest session. Also, background life stress and psychological trait variables were assessed. Compared to Low WHR subjects, High WHR subjects secreted significantly more cortisol during the stressful session after 60 minutes of stress, and considering the total area under the curve of secretion. This difference was not seen on the rest day. In terms of background and psychological measures, High WHR subjects were characterized by poorer coping skills and differences in mood reactivity. Specifically, although all subjects became more angry in response to the stressful session, High WHR subjects showed smaller increases in anger. This could indicate that they are more likely to evidence a helpless reaction to uncontrollable stress. These findings support the hypothesis that cortisol secretion might represent a mechanism for the observed association between stress and abdominal fat distribution. Furthermore, differences in coping and appraisal may suggest that a particular psychological pattern might influence the reactivity of the adrenal-cortical system to stress, and subsequent fat distribution.

Regional fat distribution and metabolism in a new mouse model (C57BL/6J) of non-insulin-dependent diabetes mellitus.

It has been suggested that a genetic predisposition and an increased total fat mass, particularly a specific increase in visceral fat, contribute to the metabolic aberrations associated with human non-insulin-dependent diabetes mellitus (NIDDM). In this study, we investigated the interactions between genetic and dietary components on fat distribution and metabolism in two mouse strains, one genetically predisposed to NIDDM (BL/6) and one not (A/J), fed either a chow diet or a high-fat, high-simple carbohydrate (HFHSC) diet for 5 months. As expected, both strains of mice fed a HFHSC diet were heavier, had more fat in both the subcutaneous (inguinal [ING] and visceral (mesenteric [MES]) regions, and had larger fat cells and higher lipoprotein lipase (LPL) activities. The results of interactions between strain and diet showed important differences in fat distribution and metabolism between strains. In comparison with A/J mice, BL/6 mice fed a HFHSC diet developed hyperglycemia, hyperinsulinemia, and hypercholesterolemia, were heavier, had more overall fat, and particularly increased their MES adipose tissue. This increase in visceral fat mass was due to an increase in fat cell number. In contrast, BL/6 mice fed a chow diet had less overall fat, a smaller MES fat pad with smaller adipocytes, and lower LPL activity than A/J controls. Significant differences between BL/6 and A/J mice fed either a HFHSC or a chow diet were not observed in ING adipose tissue. These data suggest that in BL/6 mice, changes in the metabolic characteristics of visceral fat seem to be a specific characteristic associated with the genetic predisposition for NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of chronic stress and exogenous glucocorticoids on regional fat distribution and metabolism.

It has been proposed that increased glucocorticoid hormones and decreased sex hormones affect regional fat metabolism and distribution. In the present work, it was hypothesized that chronic, uncontrollable stress, known to affect the pituitary-adrenal and pituitary-gonadal axes might, therefore, lead to differences in regional fat accumulation. In comparison with controls, male Sprague-Dawley rats stressed for 28 days, had significantly larger adipocytes. In addition, a tendency for a heavier fat pad and an increased lipoprotein lipase activity in the mesenteric depot was suggested. No significant changes were seen in epididymal, retroperitoneal, and inguinal regions. In order to study if the effects observed could be attributed to increased glucocorticoids, the response to a direct administration of supraphysiological doses of corticosterone, given either in the drinking water or via subcutaneous implantation of corticosterone pellets, was studied. Increased fat accumulation was shown in all fat depots in a dose-response fashion, but was significantly more pronounced in the mesenteric region. It was concluded that mesenteric fat tissue may respond to stress in a different manner from other fat depots. Glucocorticoids seem to be partly, but not solely, responsible for the changes observed in adipose tissue metabolism and distribution following exposure to uncontrollable stress.

Effect of testosterone on abdominal adipose tissue in men.

Recent studies in men have shown that abdominal fat increases with age and decreasing testosterone concentrations. Furthermore, in cell culture, testosterone expresses an increased lipolytic potential and depresses lipoprotein lipase activity (LPL) in adipose cells. These metabolic characteristics are found in abdominal adipose tissue in young men. In order to see whether abdominal fat masses in moderately obese middle-aged men might be diminished by testosterone, this hormone was given either as a single injection (500 mg) or in moderate doses (40 mg X 4) for 6 weeks in an oral preparation, bypassing the liver. When measured 1 week after the single dose, abdominal LPL tended to decrease. After 6 weeks a dramatic decrease of abdominal LPL was found, as well as an increase in the lipolytic responsiveness to norepinephrine, both changes confined solely to the abdominal, and not femoral adipose tissue regions. The waist/hip circumference decreased in 9 out of the 11 examined men. No untoward effects were seen in behavioural variables, blood pressure, triglyceride or cholesterol values, and liver function tests. These preliminary results suggest that administration of testosterone in moderate doses to middle-aged men lead to adaptations of the metabolism of adipose tissue expected to be followed by a diminution of this mass.

The effects of exercise, training on body composition and metabolism in men and women.

In order to examine whether there are sex-differences in the response of energy balance to physical training slightly obese men and women participated in the same 3 months physical training program with the same individual relative intensity. The men became somewhat lighter (-2 kg) and leaner (-2.9 kg body fat) and showed decreases in sum of insulin and sum of C-peptide values during an oral glucose tolerance test as well as cholesterol values. The women showed decrease of 2.6 kg body fat, and also increased lean body mass (1.9 kg) and similar metabolic changes. The women had, however, a larger body fat mass at the outset. When women with similar body fat mass as that of men were analysed separately, no change in body weight or body fat had occurred, and the metabolic adaptations were less pronounced. No compensatory increase of energy intake could be discovered in any of the groups, the most obese women actually showed a decrease. Taken together with previous information these results suggest that men, like male rats, become leaner during physical training due to a lack of energy intake compensation. Women with similar body fat mass, however, like female rats, may react with such a compensation, causing a protection of their body fat. Women usually have more body fat than men, however. Obese women in this study showed a decrease of body fat.

Effects of early pregnancy on regional adipose tissue metabolism.

Adipose tissue metabolism was studied in needle biopsies from femoral and abdominal subcutaneous depots, in 12 healthy young women, during early (9-11 weeks) pregnancy, and 6 weeks after a legal abortion. Both during pregnant and non-pregnant conditions, a higher lipoprotein lipase (LPL) activity was seen in the femoral compared to the abdominal region, but the LPL activity was not influenced by early pregnancy. Rates of fatty acid esterification and acylglyceride synthesis were not different between regions, nor affected by pregnancy. The stimulatory effect of norepinephrine (10(-7) M) on lipolysis was significantly greater in the abdominal than in the femoral region in both the pregnant and non-pregnant condition. This difference was apparently due to higher alpha-adrenergic activity in the femoral region. Pregnancy per se had no effect on lipolytic response to norepinephrine. These findings indicate that lipid accumulation is favoured in the femoral region in young women both during pregnant and non-pregnant conditions.

Steroid hormone receptors in human adipose tissues.

Administration of glucocorticoid, estrogen, and progesterone is followed by changes in human adipose tissue distribution, morphology, and function. Therefore, specific receptors for these hormones were determined in different regions of human adipose tissue using ligand techniques, with separation of bound and free hormone by chromatography, absorption techniques, or isoelectric focusing, as well as protein quantitation with monoclonal antibodies against human estrogen and progesterone receptors. Furthermore, mRNAs were measured by solubilization hybridization technique with glucocorticoid, estrogen, and progesterone receptor cRNA probes for human receptors. Saturable specific cytosolic glucocorticoid binding was found. Quantitative analyses indicated more binding sites and mRNAs in intraabdominal than sc adipose tissue samples. In contrast, neither specific estrogen or progesterone binding, cytosolic or nuclear receptor protein, nor mRNAs for these receptors could be identified in abdominal, femoral, or omental adipose tissues. Parallel control experiments confirmed the presence of both estrogen and progesterone receptors in rat adipose tissues. It was concluded that while glucocorticoid receptors are clearly present in human adipose tissues, female sex hormone receptors are not present in quantities detectable with presently available methods. Effects of these hormones on human adipose tissue might, therefore, be mediated via a minute nondetectable quantity of receptors, the glucocorticoid receptor, or indirect mechanisms.

Metabolism of adipose tissue in intraabdominal depots in severely obese men and women.

In groups of obese men and women with an abdominal type of fat distribution, we measured fat cell size, lipoprotein lipase (LPL) activity and lipolysis stimulated by norepinephrine (NE) or isoproterenol (ISO) or inhibited by insulin, in subcutaneous abdominal and retroperitoneal (nonportal), as well as in omental and mesenteric (portal) adipose tissues. Both men and women had large intraabdominal adipocytes. No differences were found between the two groups of obese subjects in fat cell size or LPL activity in the different adipose tissue regions. Women had as high NE- or ISO-stimulated lipolysis in the portal as in nonportal fat tissues, equally high as that found in men. In comparisons with a previous study in nonobese men and women, these results show an increased fat cell size in all tissues in obese women and an increased lipolysis in portal tissues in obese women and in nonportal tissues in obese men. Taken together, these results might mean that obese men and abdominally obese women have a large potential to release free fatty acids (FFA) from intraabdominal depots. This might be followed by metabolic derangements seen in such groups of obese subjects.

Regional adipose tissue metabolism in postmenopausal women after treatment with exogenous sex steroids.

In order to evaluate the effect of exogenous sex steroids on adipose tissue metabolism, two groups of postmenopausal women were studied. In one of the groups, the effect of 50 micrograms ethinyl estradiol (EE) was investigated given orally alone and in combination with 10 mg norethisterone acetate (NET). This combination is reminiscent of an old high dose oral contraceptive. In the other group, the effect of 3 mg 17 beta-estradiol was evaluated when administered percutaneously alone and in combination with 300 mg micronized progesterone given orally. These substances and doses were chosen to provide a "physiological" hormonal influence. In the femoral region 50 micrograms EE induced an increase in LPL activity. This elevated LPL value was reversed with the addition of 10 mg NET. Moreover, during treatment with 50 micrograms EE, a decrease in norepinephrine stimulated lipolysis was seen in the abdominal region. The percutaneous administration of 17 beta-estradiol with or without micronized progesterone, however, was inert as regards subcutaneous adipose tissue metabolism. Our findings indicate, therefore, that EE in doses used in oral contraception might promote lipid accumulation in the femoral adipose tissue depot.

Uptake of triglyceride fatty acids in adipose tissue in vivo in man.

Currently available information on adipose tissue metabolism in man is mainly based on studies in vitro. In the present work adipose tissue lipid uptake was studied in vivo in man. 100 g glucose and 120 g milk fat with 10 microCi U-14C oleic acid were given in the overnight fasting state to eight women and 2 h after a carbohydrate-rich meal to eight women. After 4 h, 1-day, 1 week and 1 month radioactivity levels were determined in the lipids of adipose tissue in the femoral and abdominal regions and in plasma. At 4 h 30 and 20% of the oleic acid was estimated to remain in the extracellular space in the fasted and fed groups respectively, measured in plasma. Contents of oleic acid radioactivity was higher in the abdominal than femoral region. An estimated 27 and 46 g of fat was taken up in adipose tissue of the fasted and fed groups, constituting 1/3 and 1/2 of total tissue uptake respectively. After 1 day these figures were 43 and 60 g respectively. At 1 week and 1 month adipose tissue radioactivity was increasing slowly. Lipoprotein lipase (LPL) activity in adipose tissue at 4 h was higher in the femoral than abdominal adipose tissue and higher in the fed than fasted state in the abdominal region. A significant correlation was found between uptake and LPL in abdominal adipose tissue only. These results show that uptake of fat measured in vivo is probably not necessarily reflected by LPL measurements only, suggesting other regulatory factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Weight cycling and fat distribution.

Interest in factors that promote a more abdominal fat distribution has arisen because a higher waist-to-hip circumference ratio (WHR) has been linked to several major health risks, such as cardiovascular disease and diabetes. In the present study we asked whether weight variability, produced by repeated cycles of weight gain and loss, influenced fat distribution toward a more abdominal pattern in premenopausal women. It was found that a higher WHR was significantly associated with a higher degree of weight cycling, controlling for age and parity. A significant association between BMI and WHR was found only in those subjects who were weight cyclers. In addition, number of pregnancies was also associated with a higher WHR. These findings suggest that repeated bouts of weight loss and regain may promote abdominal adiposity and consequently, may contribute to long-term health risks.

Anthropometric variables and metabolism in polycystic ovarian disease.

Anthropometric, endocrine and metabolic variables, were examined in women with polycystic ovarian syndrome (PCO), and in normal control women. Obese women with PCO had higher plasma insulin values than non obese women with PCO, but lean body mass, glucose tolerance, plasma triglycerides and blood pressure were not different in spite of almost twice the body fat mass in the obese PCO women. However, in comparisons between non-obese PCO and control women, with equal body fat mass, the PCO women had higher blood pressure, plasma triglycerides and insulin, as well as a tendency to increased lean body mass. Both PCO groups had a high waist/hip ratio and larger abdominal fat cells than controls, indicating a preferential abdominal accumulation of adipose tissue. In comparison with abdominal adipocytes, femoral adipocytes were larger and had higher lipoprotein lipase activity in the control women, while in the PCO women these regional differences were not found. Basal and norepinephrine stimulated lipolysis were higher in the abdominal than femoral adipocytes in all groups. Substitution of the PCO women with ethinyl estradiol plus desogestrel during 6 months resulted in a regression of clinical androgenic symptoms as well as a normalization of plasma concentrations of free testosterone and sex hormone binding globulin. However, neither body composition nor metabolism were normalized. It was concluded that body fat distribution is more closely related to hypertension and metabolic derangements than total fat mass in the PCO syndrome. It is suggested that the relative paucity of femoral adipose tissue is due to a lack of specific effects of progesterone on adipocytes in this region.

Metabolism of adipose tissue in intraabdominal depots of nonobese men and women.

Adipocyte size, lipoprotein lipase (LPL) activity, and the lipolytic response to noradrenaline and isoproterenol were studied in three intraabdominal depots (mesenteric, omental, retroperitoneal), as well as in subcutaneous abdominal adipose tissue, in nonobese groups of middle-aged men and in premenopausal and postmenopausal women. Subcutaneous adipocytes were larger than intraabdominal adipocytes in all groups. The men had large adipocytes in all intraabdominal depots as compared with the women. The premenopausal women seemed to have low LPL activity in intraabdominal depots. Two types of responses to catecholamine-stimulated lipolysis were observed: a similar response from mesenteric and omental (portal) fat depots and from retroperitoneal and subcutaneous abdominal (nonportal) fat depots. Young women had higher lipolysis in nonportal than in portal adipose tissues. In the men the reverse characteristics were found. These dissimilarities seem to be based on differences in beta-adrenergic responsiveness. Postmenopausal women showed no differences between depots. The differences in lipolytic responsiveness between these groups might be caused by sex steroid hormones.

Muscle and adipose tissue morphology and metabolism in Cushing's syndrome.

Femoral and abdominal adipose tissue cellularity and metabolism as well as muscle morphology and metabolism were examined in women with Cushing's syndrome and compared with those in nonobese women and obese women with the android and gynoid types of fat distribution. Cushing's syndrome was characterized by abdominal obesity and enlarged abdominal fat cells, with adipose tissue lipoprotein lipase activity elevated 2-3 times that in normal women and low lipolytic capacity. Muscle tissue in women with Cushing's syndrome had a relatively low proportion of type I (30%) and a high proportion of type IIB (32%) muscle fibers, similar to those in android obesity (45% and 25%, respectively) and in contrast to fiber composition in gynoid obesity (55% and 12%, respectively). Glycogen synthase activity in the lateral vastus muscle was very low. We suggest that the enlargement of abdominal fat depots in women with Cushing's syndrome is at least partially due to elevated adipocyte lipoprotein lipase activity and low lipolytic activity. Furthermore, the abnormal muscle fiber composition might be caused by the corticosteroid excess. Such muscle is known to be relatively insulin insensitive and might thus contribute to the marked insulin resistance that occurs during chronic corticosteroid excess.

Steroid hormones and distribution of adipose tissue.

Several descriptive studies, performed in women before and after menopause, in young and older men and in women with Cushing's disease, have suggested that steroid hormones have a role in the regulation of regional fat metabolism. Femoral lipoprotein lipase (LPL) activity seems to be increased by progesterone, while it might be inhibited by testosterone. Estradiol and testosterone might be lipolytic in the abdominal region. Long-term exposure to corticosteroid might increase femoral LPL activity and decrease abdominal lipolysis. These conclusions, however, are only tentative. Corticosteroid hormones bind to the cytosolic fraction of human adipose tissue, while no binding was observed with estradiol or progesterone. The relationship between steroid hormone receptors and biological effects in unknown. Further work should be performed to investigate the mechanisms by which steroid hormones might influence human adipose tissue metabolism and distribution.

Glucose uptake in human adipose tissue.

One hundred grams of glucose with 50 microCi U-14C-glucose were given orally to 17 women with widely varying amounts of body fat. Radioactivity and glucose metabolism in vitro were then measured in adipose tissue obtained by needle biopsies in the abdominal and femoral regions after four hours. Radioactivity in triglycerides was then measured in repeated biopsies 1 day, 1 week, and monthly up to 7 months after glucose administration. Glucose label in triglycerides after four hours was higher in abdominal than femoral adipocytes in obese women. It increased slightly during the following week, and then decreased exponentially with a half-life of 12 months in the abdominal region and 19 months in the femoral region. Uptake of glucose carbon in total body fat was estimated from the triglyceride label measured and determinations of body fat mass, and found to be in the order of less than 4% of given glucose. The studies in vitro suggested that much of the glucose taken up in adipose tissue is converted to lactate. If this is the case in vivo, then glucose uptake in adipose tissue might well be of significance for total body glucose homeostasis, particularly in obese subjects, amounting to maximally perhaps one third to one half of the oral glucose given. The majority of this glucose uptake would then, however, leave adipose tissue again as lactate. The shorter half-life of label in abdominal adipocytes is in agreement with findings of increased lipolysis in these adipocytes in vitro.