Daniel H. Bessesen

Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline

OBJECTIVEnTo formulate clinical practice guidelines for the pharmacological management of obesity.nnnPARTICIPANTSnAn Endocrine Society-appointed Task Force of experts, a methodologist, and a medical writer. This guideline was co-sponsored by the European Society of Endocrinology and The Obesity Society.nnnEVIDENCEnThis evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence.nnnCONSENSUS PROCESSnOne group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the European Society of Endocrinology, and The Obesity Society reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize some of the supporting evidence.nnnCONCLUSIONSnWeight loss is a pathway to health improvement for patients with obesity-associated risk factors and comorbidities. Medications approved for chronic weight management can be useful adjuncts to lifestyle change for patients who have been unsuccessful with diet and exercise alone. Many medications commonly prescribed for diabetes, depression, and other chronic diseases have weight effects, either to promote weight gain or produce weight loss. Knowledgeable prescribing of medications, choosing whenever possible those with favorable weight profiles, can aid in the prevention and management of obesity and thus improve health.

Resistant starch consumption promotes lipid oxidation

BackgroundAlthough the effects of resistant starch (RS) on postprandial glycemia and insulinemia have been extensively studied, little is known about the impact of RS on fat metabolism. This study examines the relationship between the RS content of a meal and postprandial/post-absorbative fat oxidation.Results12 subjects consumed meals containing 0%, 2.7%, 5.4%, and 10.7% RS (as a percentage of total carbohydrate). Blood samples were taken and analyzed for glucose, insulin, triacylglycerol (TAG) and free fatty acid (FFA) concentrations. Respiratory quotient was measured hourly. The 0%, 5.4%, and 10.7% meals contained 50 μCi [1-14C]-triolein with breath samples collected hourly following the meal, and gluteal fat biopsies obtained at 0 and 24 h. RS, regardless of dose, had no effect on fasting or postprandial insulin, glucose, FFA or TAG concentration, nor on meal fat storage. However, data from indirect calorimetry and oxidation of [1-14C]-triolein to 14CO2 showed that addition of 5.4% RS to the diet significantly increased fat oxidation. In fact, postprandial oxidation of [1-14C]-triolein was 23% greater with the 5.4% RS meal than the 0% meal (p = 0.0062).ConclusionsThese data indicate that replacement of 5.4% of total dietary carbohydrate with RS significantly increased post-prandial lipid oxidation and therefore could decrease fat accumulation in the long-term.

Effects of short-term overfeeding on hunger, satiety, and energy intake in thin and reduced-obese individuals.

BACKGROUNDnCertain individuals appear to be resistant to weight gain in an obesigenic environment, yet the mechanisms for this adaptation are unclear. These individuals may sense positive energy balance more appropriately than those individuals prone to weight gain.nnnRESEARCH METHODS AND PROCEDURESnThirteen thin (7 women, 6 men) and 9 reduced-obese (5 women, 4 men) individuals were studied. Measures of intake were obtained using visual analog scales before and after each meal during eucaloric feeding and during three days of 50% overfeeding. Ad libitum energy intake was measured post-overfeeding.nnnRESULTSnOverfeeding resulted in a significant reduction in pre-meal hunger in the thin (68+/-6 to 41+/-6 mm, p<0.0001) compared to the reduced-obese individuals (63+/-7 to 65+/-7 mm, p=0.67). There was a significantly greater increase (p=0.0016) in post-meal satiety scores during overfeeding in the thin (65+/-4 to 88+/-4 mm, p<0.0001) compared to the reduced-obese individuals (72+/-5 to 80+/-5 mm, p=0.04). Thin women had a 30% reduction in daily energy intake (1831+/-47 to 1273+/-79 kcal/day, p=0.005) after overfeeding while no difference was seen in the thin men or reduced-obese group.nnnDISCUSSIONnThin individuals appear to sense positive energy balance more appropriately with changes in measures of intake than reduced-obese individuals. These findings are especially true in thin women.

The Effects of Overfeeding on Spontaneous Physical Activity in Obesity Prone and Obesity Resistant Humans

Despite living in an environment that promotes weight gain in many individuals, some individuals maintain a thin phenotype while self‐reporting expending little or no effort to control their weight. When compared with obesity prone (OP) individuals, we wondered if obesity resistant (OR) individuals would have higher levels of spontaneous physical activity (SPA) or respond to short‐term overfeeding by increasing their level of SPA in a manner that could potentially limit future weight gain. SPA was measured in 55 subjects (23 OP and 32 OR) using a novel physical activity monitoring system (PAMS) that measured body position and movement while subjects were awake for 6 days, either in a controlled eucaloric condition or during 3 days of overfeeding (1.4× basal energy) and for the subsequent 3 days (ad libitum recovery period). Pedometers were also used before and during use of the PAMS to provide an independent measure of SPA. SPA was quantified by the PAMS as fraction of recording time spent lying, sitting, or in an upright posture. Accelerometry, measured while subjects were in an upright posture, was used to categorize time spent in different levels of movement (standing, walking slowly, quickly, etc.). There were no differences in SPA between groups when examined across all study periods (P > 0.05). However, 3 days following overfeeding, OP subjects significantly decreased the amount of time they spent walking (−2.0% of time, P = 0.03), whereas OR subjects maintained their walking (+0.2%, P > 0.05). The principle findings of this study are that increased levels of SPA either during eucaloric feeding or following short term overfeeding likely do not significantly contribute to obesity resistance although a decrease in SPA following overfeeding may contribute to future weight gain in individuals prone to obesity.

Relationship of abdominal obesity measured by DXA and waist circumference with insulin sensitivity in Hispanic and non‐Hispanic white individuals: The San Luis Valley Diabetes Study

To determine if dual‐energy X‐ray absorptiometry (DXA) measures of trunk fat, a user‐defined abdominal region of interest (ROI) and waist circumference (WC) differ in their association with insulin sensitivity among Hispanics and non‐Hispanic whites (NHW) or explain any ethnic differences in insulin sensitivity.

Regulation of body weight: what is the regulated parameter?

Despite dramatic variations in day to day intake and energy expenditure, weight remains relatively stable in most animals and humans. There are clear physiological responses to over and underfeeding suggesting that the body strives to maintain a constant weight. Despite this, for most humans and experimental animals, there is a tendency for weight to increase slowly over the lifespan. Recent increases in the prevalence of both obesity and anorexia nervosa suggest that factors other than homeostatic physiological mechanisms are important in determining body weight. Clearly reward pathways are activated by palatable food and evidence is emerging that energy balance can modulate these reward pathways and alter the salience of food related stimuli. Significant inhibitory control of reward pathways also comes from a number of brain regions involved in regulation of behavior. Finally there is strong evidence of the important role that social and environmental factors play in modulating both food intake and physical activity behaviors which in turn result in alterations in weight over time. While some aspects of these regulatory systems are within the conscious awareness of people, many, perhaps even most are not. The evidence then would suggest that weight is controlled by several complex regulatory systems that respond to internal metabolic and hormonal signals, hedonic properties of food, internal forces of valuation and self-control, and social factors. Each of these systems is likely regulated and is important in ultimately determining body weight. Experimental paradigms that test one variable in one of these interrelated systems should, where possible control or at least consider the other systems in an effort to provide an integrated picture of weight regulation.

Adrenergic control of lipolysis in women compared with men

Data suggest women are more sensitive to the lipolytic action of epinephrine compared with men while maintaining similar glucoregulatory effects (Horton et al. J Appl Physiol 107: 200-210, 2009). This study aimed to determine the specific adrenergic receptor(s) that may mediate these sex differences. Lean women (n = 14) and men (n = 16) were studied on 4 nonconsecutive days during the following treatment infusions: saline (S: control), epinephrine [E: mixed β-adrenergic (lipolytic) and α2-adrenergic (antilipolytic) stimulation], epinephrine + phentolamine (E + P: mixed β-adrenergic stimulation only), and terbutaline (T: selective β2-adrenergic stimulation). Tracer infusions of glycerol, palmitate, and glucose were administered to determine systemic lipolysis, free fatty acid (FFA) release, and glucose turnover, respectively. Following basal measurements, substrate and hormone concentrations were measured in all subjects over 90 min of treatment and tracer infusion. Women had greater increases in glycerol and FFA concentrations with all three hormone infusions compared with men (P < 0.01). Glycerol and palmitate rate of appearance (Ra) and rate of disappearance (Rd) per kilogram body weight were greater with E infusion in women compared with men (P < 0.05), whereas no sex differences were observed with other treatments. Glucose concentration and kinetics were not different between sexes with any infusion. In conclusion, these data support the hypothesis that the greater rate of lipolysis in women with infusion of E was likely due to lesser α2 antilipolytic activation. These findings may help explain why women have greater lipolysis and fat oxidation during exercise, a time when epinephrine concentration is elevated.

Twenty-Four Hour Total and Dietary Fat Oxidation in Lean, Obese and Reduced-Obese Adults with and without a Bout of Exercise

Background It has been hypothesized that obese and reduced-obese individuals have decreased oxidative capacity, which contributes to weight gain and regain. Recent data have challenged this concept. Objective To determine (1) whether total and dietary fat oxidation are decreased in obese and reduced-obese adults compared to lean but increase in response to an acute exercise bout and (2) whether regular physical activity attenuates these metabolic alterations. Design We measured 24-hr total (whole-room calorimetry) and dietary fat (14C-oleate) oxidation in Sedentary Lean (BMIu200a=u200a21.5±1.6; nu200a=u200a10), Sedentary Obese (BMIu200a=u200a33.6±2.5; nu200a=u200a9), Sedentary Reduced-Obese (RED-SED; BMIu200a=u200a26.9±3.7; nu200a=u200a7) and in Physically Active Reduced-Obese (RED-EX; BMIu200a=u200a27.3±2.8; nu200a=u200a12) men and women with or without an acute exercise bout where energy expended during exercise was not replaced. Results Although Red-SED and Red-EX had a similar level of fatness, aerobic capacity and metabolic profiles were better in Red-EX only compared to Obese subjects. No significant between-group differences were seen in 24-hr respiratory quotient (RQ, Lean: 0.831±0.044, Obese: 0.852±0.023, Red-SED: 0.864±0.037, Red-EX: 0.842±0.039), total and dietary fat oxidation. A single bout of exercise increased total (+27.8%, p<0.0001) and dietary (+6.6%, pu200a=u200a0.048) fat oxidation across groups. Although exercise did not impact RQ during the day, it decreased RQ during sleep (pu200a=u200a0.01) in all groups. Red-EX oxidized more fat overnight than Red-SED subjects under both resting (pu200a=u200a0.036) and negative energy balance (pu200a=u200a0.003) conditions, even after adjustment for fat-free mass. Conclusion Obese and reduced-obese individuals oxidize as much fat as lean both under eucaloric and negative energy balance conditions, which does not support the hypothesis of reduced oxidative capacity in these groups. Reduced-obese individuals who exercise regularly have markers of metabolic health similar to those seen in lean adults. Both the acute and chronic effects of exercise were primarily observed at night suggesting an important role of sleep in the regulation of lipid metabolism.

Postprandial triglycerides and adipose tissue storage of dietary fatty acids: Impact of menopause and estradiol

Postprandial lipemia worsens after menopause, but the mechanism remains unknown. The hypothesized menopause‐related postprandial lipemia would be (1) associated with reduced storage of dietary fatty acids (FA) as triglyceride (TG) in subcutaneous adipose tissue (SAT) and (2) improved by short‐term estradiol (E2).

Brown fat activity is not apparent in subjects with HIV lipodystrophy and increased resting energy expenditure.

The HIV lipodystrophy (LD) syndrome is associated with increased resting energy expenditure (REE), but the basis of this hypermetabolism has not been determined. The objective of this pilot study was to determine if brown fat is activated in subjects with HIV LD and increased REE. In this descriptive study of four subjects with HIV LD and marked hypermetabolism, REE was measured by indirect calorimetry and brown fat activity was determined by 18F‐fluorodeoxyglucose (FDG) positron‐emission tomography (PET) combined with anatomic computed tomography (CT). Brown fat activity was not apparent in any subject with HIV LD and resting hypermetabolism. Therefore, brown fat activation is unlikely to be the principal cause of the increased REE associated with the HIV LD syndrome. Evidence of adaptive thermogenesis has been demonstrated in this syndrome, but this study suggests that tissues other than brown adipose tissue (BAT) are responsible. Further understanding of the chronic hypermetabolism associated with HIV LD could provide new insights into the regulation of energy balance.