MRI characterization of brown adipose tissue under thermal challenges in normal weight, overweight, and obese young men.

PURPOSE: To implement quantitative Dixon magnetic resonance imaging (MRI) methods for brown adipose tissue (BAT) characterization at inactive and cold-activated states in normal weight, overweight, and obese subjects. The hypotheses are that MRI characteristics of BAT would differentiate between nonobese and obese subjects, and activation of BAT in response to thermal challenges that are detected by MRI would be correlated with BAT activity measured by positron emission tomography / computed tomography (PET/CT). MATERIALS AND METHODS: Fifteen male subjects (20.7 ± 1.5 years old) including six normal weight, five overweight, and four obese subjects participated in the study. A multiecho Dixon MRI sequence was performed on a 1.5T scanner. MRI was acquired under thermoneutral, nonshivering thermogenesis, and subsequent warm-up conditions. Fat fraction (FF), R2*, and the number of double bonds (ndb) were measured by solving an optimization problem that fits in- and out-of-phase MR signal intensities to the fat-water interference models. Imaging acquisition and postprocessing were performed by two MRI physicists. In each subject, Dixon MRI measurements of FF, R2*, and ndb were calculated for each voxel within all BAT regions of interest (ROIs) under each thermal condition. Mean FF, R2*, and ndb were compared between nonobese (ie, normal-weight/overweight) and obese subjects using the two-sample t-test. Receiver operating characteristic (ROC) analyses were performed to differentiate nonobese vs. obese subjects. BAT MRI measurement changes in response to thermal condition changes were compared with hypermetabolic BAT volume/activity measured by PET/CT using the Pearson's correlation. In addition, BAT MRI measurements were compared with body adiposity using the Pearson's correlation. P < 0.05 was considered statistically significant. RESULTS: Obese subjects showed higher FF and lower R2* than nonobese subjects under all three thermal conditions (P < 0.01). ROC analyses demonstrated that FF and R2* were excellent predictors for the differentiation of nonobese from obese subjects (100% specificity and 100% sensitivity). FF changes under thermal challenges were correlated with hypermetabolic BAT volume (r = -0.55, P = 0.04 during activation, and r = 0.72, P = 0.003 during deactivation), and with BAT activity (r = 0.69, P = 0.006 during deactivation), as measured by PET/CT. FF and R2* under all three thermal conditions were highly correlated with body adiposity (P ≤ 0.002). CONCLUSION: MRI characteristics of BAT differentiated between nonobese and obese subjects in both inactivated and activated states. BAT activation detected by Dixon MRI in response to thermal challenges were correlated with glucose uptake of metabolically active BAT. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:936-947.

Activated brown adipose tissue and its relationship to adiposity and metabolic markers: an exploratory study.

Objective: To explore relationships between PET/CT characteristics of cold-activated brown adipose tissue (BAT), measures of adiposity and metabolic markers.Methods: We conducted a post-hoc analysis of a study which utilized PET/CT to characterize BAT. 25 men ages 18-24 (BMI 19.4 to 35.9 kg/m2) were studied. Fasting blood samples were collected. Body composition was measured using DXA. An individualized cooling protocol was utilized to activate BAT prior to imaging with PET/CT.Results: There was an inverse relationship between fasting serum glucose and BAT volume (r = -0.40, p = 0.048). A marginally significant inverse relationship was also noted between fasting glucose and total BAT activity (r = -0.40, p = 0.05). In addition, a positive correlation was observed between serum FGF21 and SUVmax (r = 0.51, p = 0.01). No significant correlations were noted for measures of BAT activity or volume and other indicators of adiposity or glucose metabolism.Conclusions: The presence of active BAT may be associated with lower fasting glucose in young men. BAT activity may also be correlated with levels of FGF21, suggesting that BAT may lower glucose levels via an FGF21 dependent pathway. Further studies are needed to clarify mechanisms by which BAT may impact glucose metabolism.

Do the obese have lower body temperatures? A new look at a forgotten variable in energy balance.

Understanding the pathogenesis of obesity is now more important than ever, given the remarkable world-wide epidemic. This paper explores the potential role of core temperature in energy balance, and develops the hypothesis that basal temperature and changes in the temperature response in various situations contribute to the enhanced metabolic efficiency of the obese state. The argument is based on the important contribution that heat production makes in establishing the basal or resting metabolic rate, as well as on an analysis of the adaptive role played by changes in temperature in response to environmental challenge. If this hypothesis is validated, new therapeutic approaches may ensue.

Core body temperature is lower in postmenopausal women than premenopausal women: potential implications for energy metabolism and midlife weight gain.

OBJECTIVE: Weight gain during the menopausal transition is common. Although studies have suggested that weight gain is more likely related to aging than menopause, there is a reduction in resting energy expenditure with surgical or natural menopause which is independent of age and changes in body composition. The underlying mechanisms could include a reduction in core body temperature. METHODS: Data were obtained from two related studies. Sample size was 23 men and 25 women (12 premenopausal,13 postmenopausal). In the Clinical Research Unit, core temperature was measured every minute for 24 hours (CorTemp System,HQ Inc.). RESULTS: Mean 24-hour core body temperature was 0.25 ± 0.06 °C lower in postmenopausal than premenopausal women (p=0.001). Mean 24-hour core temperature was 0.34 ± 0.05 °C lower in men than in premenopausal women (p<0.001). CONCLUSIONS: Postmenopausal women, like men, had lower core body temperatures than premenopausal women. This may have implications for midlife weight gain.

Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment--a position paper of the The Obesity Society and The American Society of Hypertension.

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The American Society of Hypertension agreed to jointly sponsor a position paper on obesity-related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced-based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients.

Obesity-related hypertension: pathogenesis, cardiovascular risk, and treatment: a position paper of The Obesity Society and the American Society of Hypertension.

In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and the American Society of Hypertension agreed to jointly sponsor a position paper on obesity-related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced-based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients.

24-h core temperature in obese and lean men and women.

Maintenance of core temperature is a major component of 24-h energy expenditure, and its dysregulation could contribute to the pathophysiology of obesity. The relationship among temperature, sex, and BMI, however, has not been fully elucidated in humans. This study investigated core temperature in obese and lean individuals at rest, during 20-min exercise, during sleep, and after food consumption. Twelve lean (18.5-24.9 kg/m(2)) and twelve obese (30.0-39.9 kg/m(2)) healthy participants, ages 25-40 years old, were admitted overnight in a clinical research unit. Females were measured in the follicular menstrual phase. Core temperature was measured every minute for 24 h using the CorTemp system, a pill-sized sensor that measures core temperature while in the gastrointestinal tract and delivers the measurement via a radio signal to an external recorder. Core temperature did not differ significantly between the obese and lean individuals at rest, postmeals, during exercise, or during sleep (P > 0.5), but core temperature averaged over the entire study was significantly higher (0.1-0.2 °C) in the obese (P = 0.023). Each individual's temperature varied considerably during the study, but at all times, and across the entire study, women were ~0.4 °C warmer than men (P < 0.0001). These data indicate that obesity is not associated with a lower core temperature but that women have a higher core temperature than men at rest, during sleep, during exercise, and after meals.

Is obesity associated with lower body temperatures? Core temperature: a forgotten variable in energy balance.

The global increase in obesity, along with the associated adverse health consequences, has heightened interest in the fundamental causes of excessive weight gain. Attributing obesity to "gluttony and sloth", blaming the obese for overeating and limiting physical activity, oversimplifies a complex problem, since substantial differences in metabolic efficiency between lean and obese have been decisively demonstrated. The underlying physiological basis for these differences have remained poorly understood. The energetic requirements of homeothermy, the maintenance of a constant core temperature in the face of widely divergent external temperatures, accounts for a major portion of daily energy expenditure. Changes in body temperature are associated with significant changes in metabolic rate. These facts raise the interesting possibility that differences in core temperature may play a role in the pathophysiology of obesity. This review explores the hypothesis that lower body temperatures contribute to the enhanced metabolic efficiency of the obese state.

A teleological view of obesity, diabetes and hypertension.

1. The current worldwide epidemic of obesity and its major complications, namely type 2 diabetes and hypertension, is well documented. The present mini-review develops the thesis that 'thrifty' metabolic traits, evolved in the setting of intermittent famine, contribute to the obesity pandemic. 2. These thrifty traits, namely a decreased capacity for dietary thermogenesis and an increased resistance to insulin-mediated glucose uptake in skeletal muscle, would prolong survival during famine but predispose to obesity and diabetes in the face of abundance. The regulation of dietary thermogenesis by the sympathetic nervous system also explains the well-established association between obesity and high blood pressure. 3. These observations provide a deep-seated rationale for the efficacy of lifestyle interventions in the treatment of obesity and its complications and may also provide a predicate for the development of new therapeutic strategies aimed at neutralizing the impact of these thrifty traits. Such strategies may entail, for example, therapeutic agents that enhance metabolic rate during low-energy diets, thereby reversing the physiological impediment imposed by suppression of the sympathetic nervous system.

Feast or famine: the sympathetic nervous system response to nutrient intake.

: 1. The use of tritiated norepinephrine (NE) to measure the turnover rate of NE in sympathetically innervated organs was pioneered in the laboratory of Julius Axelrod. This technique provides an organ specific assessment of sympathetic activity, integrated over a 24 h period, in free living laboratory animals. As such it has proved useful in estimating changes in sympathetic outflow in different physiologic and patho-physiologic states. 2. Studies employing NE turnover techniques in laboratory rodents have demonstrated conclusively that fasting suppresses and overfeeding stimulates the sympathetic nervous system (SNS). These changes in sympathetic activity also occur in humans. 3. Diet-induced changes in SNS activity are regulated by insulin-mediated glucose uptake and metabolism in central neurons sensitive to insulin and located anatomically in the ventro-medial hypothalamus. The regulation is imposed by descending inhibition of tonically active sympathetic brainstem centers. 4. Diet-induced changes in SNS activity mediate changes in energy production known as dietary thermogenesis. The capacity for dietary thermogenesis serves as a potential buffer against weight gain.5. Insulin stimulated SNS activity contributes to obesity-related hypertension. The insulin resistance of obesity, and consequent hyperinsulinemia, drives sympathetically mediated thermogenesis, restoring energy balance at the expense of SNS over activity. The association of obesity and hypertension, therefore, may be the unintended consequence of mechanisms recruited in the obese to limit further weight gain.

Sympathetic nervous system activity in rat thyroid: potential role in goitrogenesis.

The role of sympathetic innervation in regulation of thyroid function is incompletely understood. We, therefore, carried out studies in rats utilizing techniques of norepinephrine turnover to assess thyroid sympathetic activity in vivo. Thyroidal sympathetic activity was increased 95% by exposure to cold (4 degrees C), 42% by chronic ingestion of an iodine-deficient diet, and 32% in rats fed a goitrogenic diet (low-iodine diet supplemented with propylthiouracil). In addition, fasting for 2 days reduced sympathetic nervous system activity in thyroid by 38%. Thyroid growth and 125I uptake were also compared in intact and decentralized hemithyroids obtained from animals subjected to unilateral superior cervical ganglion decentralization. Unilateral superior cervical ganglion decentralization led to a reduction in thyroid weight, in 125I uptake by thyroid tissue, and in TSH-induced stimulation of 125I uptake in decentralized hemithyroids. These results suggest that sympathetic activity in thyroid contributes to gland enlargement and may modulate tissue responsiveness to TSH.

Diabetes and hypertension: pathogenesis, prevention and treatment.

Hypertension occurs in approximately 30% of patients with type 1 diabetes and from 50 to 80% of patients with type 2 diabetes. Although the pathogenesis of hypertension is distinct in each type, hypertension markedly enhances the already high risk of cardiovascular and renal disease in types 1 and 2 and implications for treatment are similar in both. The threshold for blood pressure treatment in diabetic patients is generally agreed to be 140/90 mm/hg with a target BP of < 130/80. So-called "lifestyle modifications" play an important role in therapy, particularly in type 2 patients, by decreasing blood pressure and improving other risk factors for cardiovascular disease. Indeed non-pharmacologic interventions have been demonstrated to prevent the development of type 2 diabetes in patients at high risk to develop the disease. Aggressive anti-hypertensive drug treatment is warranted given the high risk associated with the combination of diabetes and hypertension and the demonstrated effectiveness of anti-hypertensive treatment in reducing cardiovascular morbidity and mortality in this group of patients. ACE inhibitors and ARBs are the cornerstones of pharmacologic management, in no small part because of the renoprotective effects of these agents in antagonizing the development and progression of diabetic renal disease. Multiple agents, including diuretics, will usually be required to attain target blood pressure levels.

Associations between repression, general maladjustment, body weight, and body shape in older males: the Normative Aging Study.

We examined relationships between repression, general maladjustment, body mass index (BMI), and waist-to-hip ratio (WHR). The participants were 1,081 healthy older men from the Normative Aging Study. Repression and General Maladjustment Scales of the Minnesota Multiphasic Personality Inventory were composite measures of personality. Repression was associated with lower BMI and WHR, and maladjustment with higher BMI and WHR. However, associations between WHR and personality dimensions were no longer significant when controlling for BMI, but associations between BMI and personality dimensions remained significant when controlling for WHR. These effects were explained by differing relationships between WHR, repression, and maladjustment for normal weight, overweight, and obese individuals. Specifically, associations between repression, maladjustment, and body shape were significant for normal weight and overweight individuals, but not for obese individuals. Health behaviors including smoking did not mediate relationships between repression, maladjustment, and body shape, but might be considered in future studies as mechanisms underlying links between personality and body shape.