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1.
Lorcaserin and Renal Outcomes in Obese and Overweight Patients in the CAMELLIA-TIMI 61 Trial.
Scirica, BM, Bohula, EA, Dwyer, JP, Qamar, A, Inzucchi, SE, McGuire, DK, Keech, AC, Smith, SR, Murphy, SA, Im, K, et al
Circulation. 2019;(3):366-375
Abstract
BACKGROUND Obesity is thought to increase renal hyperfiltration, thereby increasing albuminuria and the progression of renal disease. The effect of pharmacologically mediated weight loss on renal outcomes is not well-described. Lorcaserin, a selective serotonin 2C receptor agonist that promotes appetite suppression, led to sustained weight loss without any increased risk for major adverse cardiovascular (CV) events in the CAMELLIA-TIMI 61 trial (Cardiovascular and Metabolic Effects of Lorcaserin in Overweight and Obese Patients-Thrombolysis in Myocardial Infarction 61). METHODS CAMELLIA-TIMI 61 randomly assigned 12 000 overweight or obese patients with or at high risk for atherosclerotic CV disease to lorcaserin or placebo on a background of lifestyle modification. The primary renal outcome was a composite of new or worsening persistent micro- or macroalbuminuria, new or worsening chronic kidney disease, doubling of serum creatinine, end-stage renal disease, renal transplant, or renal death. RESULTS At baseline, 23.8% of patients had an estimated glomerular filtration rate (eGFR) <60 mL·min-1·1.73 m-2 and 19.0% had albuminuria (urinary albumin:creatinine ratio ≥30 mg/g). Lorcaserin reduced the risk of the primary renal composite outcome (4.2% per year versus 4.9% per year; hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96; P=0.0064). The benefit was consistent across subpopulations at increased baseline CV and renal risk. Lorcaserin improved both eGFR and urinary albumin:creatinune ratio within the first year after randomization. The effect of lorcaserin on weight, hemoglobin A1c, and systolic blood pressure was consistent regardless of baseline renal function. Likewise, there was no excess in cardiovascular events in patients assigned to lorcaserin in comparison with placebo, regardless of renal function. After adjustment for baseline characteristics, those with evidence of kidney disease were at increased risk of major CV events. Compared with patients with an eGFR ≥90 mL·min-1·1.73 m-2, those with an eGFR 60-90 and those <60 mL·min-1·1.73 m-2 had HRs of 1.25 (95% CI, 1.01, 1.56) and 1.51 (95% CI, 1.17, 1.95), respectively ( P for trend 0.0015). Likewise, compared with patients with no albuminuria (<30 mg/g), those microalbuminuria and those with macroalbuminuria had HRs of 1.46 (95% CI, 1.22, 1.74) and 2.10 (95% CI, 1.58, 2.80), respectively ( P for trend <0.0001). CONCLUSIONS Renal dysfunction was associated with increased CV risk in overweight and obese patients. When added to diet and lifestyle, lorcaserin reduced the rate of new-onset or progressive renal impairment in comparison with placebo. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT02019264.
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Six Weeks of Morning Fasting Causes Little Adaptation of Metabolic or Appetite Responses to Feeding in Adults with Obesity.
Chowdhury, EA, Richardson, JD, Gonzalez, JT, Tsintzas, K, Thompson, D, Betts, JA
Obesity (Silver Spring, Md.). 2019;(5):813-821
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Abstract
OBJECTIVE The aim of this study was to determine the effects of sustained morning fasting or breakfast consumption on metabolism, energy intake, and appetite in healthy adults with obesity. METHODS An independent-measures randomized controlled trial with baseline and follow-up laboratory assessment days separated by a 6-week intervention of either morning fasting (0 kcal until 12:00 pm) or daily breakfast (> 700 kcal by 11:00 am) was performed. Measures included metabolic outcomes (glucose, insulin, nonesterified fatty acids), hormones regulating appetite (total/acylated ghrelin, peptide YY, leptin), and energy expenditure (diet-induced thermogenesis) parameters throughout a laboratory test day and ad libitum intake following a fixed breakfast. RESULTS Allocation to fasting versus breakfast resulted in minimal adaptation as reflected by the metabolic outcomes or the majority of appetite regulatory outcomes for either area under curve or time-course-based measures (P > 0.05). Ad libitum lunch intake was not different (P = 0.13), nor was diet-induced thermogenesis or a composite appetite score (both P > 0.10). However, there was a reduced total area under the curve for peptide YY (P = 0.05) and increased postprandial hunger ratings (P = 0.05) in the breakfast group. CONCLUSIONS There was little evidence of metabolic adaptation to acute feeding or negative consequences from sustained morning fasting. This indicates that previously observed differences between breakfast consumers and skippers may be acute effects of feeding or may have resulted from other lifestyle factors.
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Appetite Regulations After Sprint Exercise Under Hypoxic Condition in Female Athletes.
Kojima, C, Kasai, N, Ishibashi, A, Murakami, Y, Ebi, K, Goto, K
Journal of strength and conditioning research. 2019;(7):1773-1780
Abstract
Kojima, C, Kasai, N, Ishibashi, A, Murakami, Y, Ebi, K, and Goto, K. Appetite regulations after sprint exercise under hypoxic condition in female athletes. J Strength Cond Res 33(7): 1773-1780, 2019-The present study determined changes in appetite-regulating hormones and energy intake after high-intensity interval exercise (HIIT) under hypoxic conditions (HYP) in trained female athletes. Fifteen female athletes completed 3 trials on different days of either HIIT under HYP, HIIT under normoxic conditions (NOR), or rest in normoxia (CON). Exercise trials consisted of 2 successive sets of 8 repeated bouts of a 6-second maximal sprint separated by a 30-second rest. Blood samples were obtained to measure plasma acylated ghrelin, glucagon-like peptide-1 (GLP-1), and metabolite concentrations. Energy intake during an ad libitum buffet meal test was evaluated 30 minutes after exercise or rest. Plasma acylated ghrelin concentrations decreased significantly after exercise (p ≤ 0.001), but no difference was observed between the HYP and NOR. Plasma GLP-1 concentrations did not differ after exercise, with no difference between the HYP and NOR. Although absolute energy intake in the HYP (634 ± 67 kcal) and NOR (597 ± 63 kcal) was significantly lower than that in the CON (756 ± 63 kcal, p = 0.006), no difference was observed between the HYP and NOR. These results show that HIIT under hypoxic and NOR lowered plasma acylated ghrelin concentrations and energy intake.
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Appetite-Suppressing and Satiety-Increasing Bioactive Phytochemicals: A Systematic Review.
Stuby, J, Gravestock, I, Wolfram, E, Pichierri, G, Steurer, J, Burgstaller, JM
Nutrients. 2019;(9)
Abstract
The prevalence of obesity is increasing worldwide. Bioactive phytochemicals in food supplements are a trending approach to facilitate dieting and to improve patients' adherence to reducing food and caloric intake. The aim of this systematic review was to assess efficacy and safety of the most commonly used bioactive phytochemicals with appetite/hunger-suppressing and/or satiety/fullness-increasing properties. To be eligible, studies needed to have included at least 10 patients per group aged 18 years or older with no serious health problems except for overweight or obesity. Of those studies, 32 met the inclusion criteria, in which 27 different plants were tested alone or as a combination, regarding their efficacy in suppressing appetite/hunger and/or increasing satiety/fullness. The plant extracts most tested were derived from Camellia sinensis (green tea), Capsicum annuum, and Coffea species. None of the plant extracts tested in several trials showed a consistent positive treatment effect. Furthermore, only a few adverse events were reported, but none serious. The findings revealed mostly inconclusive evidence that the tested bioactive phytochemicals are effective in suppressing appetite/hunger and/or increasing satiety/fullness. More systematic and high quality clinical studies are necessary to determine the benefits and safety of phytochemical complementary remedies for dampening the feeling of hunger during dieting.
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Effects of active commuting and leisure-time exercise on appetite in individuals with overweight and obesity.
Quist, JS, Blond, MB, Gram, AS, Steenholt, CB, Janus, C, Holst, JJ, Rehfeld, JF, Sjödin, A, Stallknecht, B, Rosenkilde, M
Journal of applied physiology (Bethesda, Md. : 1985). 2019;(4):941-951
Abstract
Acute exercise is associated with a transient suppression of appetite. The effects of regular exercise on appetite are not well understood. We aimed to determine the effects of active commuting and leisure-time exercise on appetite. One hundred thirty physically inactive women and men (20-45 yr) with overweight and obesity were randomized to 6 mo of habitual lifestyle (CON, n = 18), active commuting (BIKE, n = 35), or leisure-time exercise of moderate [MOD, 50% peak oxygen uptake (V̇o2peak)-reserve, n = 39] or vigorous (VIG, 70% V̇o2peak-reserve, n = 38) intensity. Appetite ratings, acylated ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucagon were assessed in the basal state and in response to meal and exercise challenges at baseline and 3 and 6 mo. Ad libitum energy intake was determined during test meals. Data from 90 participants (per protocol) were available, and results are comparisons with CON. At 3 mo, ad libitum energy intake was lower in VIG (-22%, P < 0.01), basal glucagon was lower in BIKE ( P < 0.05) and VIG ( P = 0.01), and postprandial ratings of prospective food consumption were lower in MOD ( P = 0.02) and VIG ( P < 0.001). In VIG, ratings of hunger ( P = 0.01) and prospective food consumption ( P = 0.03) were lower after acute exercise at 3 mo. At 6 mo, basal and postprandial GLP-1 were higher ( P ≤ 0.04) whereas postexercise PYY was lower ( P = 0.03) in VIG and postexercise CCK was lower in BIKE ( P = 0.03). Vigorous-intensity exercise training leads to a transient suppression of energy intake and subjective appetite (3 mo) but a more long-term increase in basal and postprandial GLP-1 (6 mo) in individuals with overweight and obesity. NEW & NOTEWORTHY This is the first randomized controlled trial, to our knowledge, investigating long-term effects of exercise domain and intensity on subjective and hormonal markers of appetite and ad libitum energy intake in individuals with overweight and obesity. Appetite was assessed in response to meal and exercise challenges at baseline and at 3 and 6 mo. Anorexigenic effects of exercise vary with the duration of intervention and are restricted to regular leisure-time exercise of vigorous intensity in individuals with overweight and obesity.
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Growth hormone therapy in children with idiopathic short stature - the effect on appetite and appetite-regulating hormones: a pilot study.
Yackobovitch-Gavan, M, Gat-Yablonski, G, Shtaif, B, Hadani, S, Abargil, S, Phillip, M, Lazar, L
Endocrine research. 2019;(1-2):16-26
Abstract
AIM: To investigate the effect of growth hormone (GH) therapy on appetite-regulating hormones and to examine the association between these hormones and the response to GH, body composition, and resting energy expenditure (REE). METHODS Nine pre-pubertal children with idiopathic short stature underwent a standard meal test before and 4 months following initiation of GH treatment. Ghrelin, GLP-1, leptin, and insulin levels were measured; area under the curve (AUC) was calculated. Height, weight, body composition, REE, and insulin-like growth factor levels were recorded at baseline and after 4 and 12 months. RESULTS Following 4 months of GH therapy, food intake increased, with increased height-standard deviation score (SDS), weight-SDS, and REE (p < .05). Significant changes in appetite-regulating hormones included a decrease in postprandial AUC ghrelin levels (p = .045) and fasting GLP-1 (p = .038), and an increase in fasting insulin (p = .043). Ghrelin levels before GH treatment were positively correlated with the changes in weight-SDS (fasting: r = .667, p = .05; AUC: r = .788, p = .012) and REE (fasting: r = .866, p = .005; AUC: r = .847, p = .008) following 4 months of GH therapy. Ghrelin AUC at 4 months was positively correlated with the changes in height-SDS (r = .741, p = .022) and fat-free-mass (r = .890, p = .001) at 12 months of GH treatment. CONCLUSIONS The reduction in ghrelin and GLP-1 following GH treatment suggests a role for GH in appetite regulation. Fasting and meal-AUC ghrelin levels may serve as biomarkers for predicting short-term (4 months) changes in weight and longer term (12 months) changes in height following GH treatment. The mechanisms linking GH with changes in appetite-regulating hormones remain to be elucidated. ABBREVIATIONS SDS: standard deviation score; REE: resting energy expenditure; SMT: standard meal test; AUC: area under the curve; ISS: idiopathic short stature; SGA: small for gestational age; FFM: fat-free-mass; FM: fat mass; EER: estimated energy requirements; DRI: dietary reference intakes; IQR: inter-quartile range.
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Oleoylethanolamide: A novel pharmaceutical agent in the management of obesity-an updated review.
Laleh, P, Yaser, K, Alireza, O
Journal of cellular physiology. 2019;(6):7893-7902
Abstract
Obesity as a multifactorial disorder has been shown a dramatically growing trend recently. Besides genetic and environmental factors, dysregulation of the endocannabinoid system tone is involved in the pathogenesis of obesity. This study reviewed the potential efficacy of Oleoylethanolamide (OEA) as an endocannabinoid-like compound in the energy homeostasis and appetite control in people with obesity. OEA as a lipid mediator and bioactive endogenous ethanolamide fatty acid is structurally similar to the endocannabinoid system compounds; nevertheless, it is unable to induce to the cannabinoid receptors. Unlike endocannabinoids, OEA negatively acts on the food intake and suppress appetite via various mechanisms. Indeed, OEA as a ligand of PPAR-α, GPR-119, and TRPV1 receptors participates in the regulation of energy intake and energy expenditure, feeding behavior, and weight gain control. OEA delays meal initiation, reduces meal size, and increases intervals between meals. Considering side effects of some approaches used for the management of obesity such as antiobesity drugs and surgery as well as based on sufficient evidence about the protective effects of OEA in the improvement of common abnormalities in people with obese, its supplementation as a novel efficient and FDA approved pharmaceutical agent can be recommended.
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Brain Stimulation to Modulate Food Intake and Eating Behavior.
Dendy, R, Stinson, EJ, Guerithault, N, Gluck, ME
Current diabetes reports. 2019;(12):152
Abstract
PURPOSE OF REVIEW Appetitive behaviors are mediated through homeostatic and reward signaling of brain circuits. There has been increasing interest in the use of neuromodulation techniques aimed at targeting brain regions such as the lateral prefrontal and subcortical regions associated with dysregulation of eating behaviors. RECENT FINDINGS Invasive brain stimulation techniques have demonstrated promising results in treating severe and enduring anorexia nervosa and morbid obesity. In addition, non-invasive techniques have been shown to successfully reduce food craving, hunger ratings, and calorie intake as well as binge/purge symptoms in eating disorders. Brain stimulation offers promising results for treating symptoms associated with eating disorders and modifying appetitive behaviors including craving and caloric consumption. Future research should focus on identifying optimal frequency and duration of stimulation and employ longitudinal studies to assess long-term effectiveness on clinical outcomes such as eating disorder symptomatology, weight loss, and sustained improvements in eating behaviors over time.
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Development of a delayed-release nutrient for appetite control in adults with obesity and type 2 diabetes and initial clinical testing in a single dose randomized controlled trial.
Beale, E, Lim, E, Yassine, H, Azen, C, Christopher, C
Nutrition & diabetes. 2019;(1):20
Abstract
BACKGROUND AND OBJECTIVES Delivery of nutrients directly to the small intestine, either via enteral feeding tube or by gastric bypass surgery, is associated with increased levels of appetite-suppressing and glucoregulatory hormones, including GLP-1, and reduced appetite. Achieving these changes non-invasively using formulated foods may be of therapeutic benefit in individuals with obesity and related comorbidities. The aim of this pilot study was to determine the effect of a single dose of a novel delayed-release nutrient (DRN) on glucose, GLP-1, c-peptide, insulin, and appetite in adults with obesity and type 2 diabetes. SUBJECTS AND METHODS We formulated an all-natural, generally recognized as safe ('GRAS") DRN and conducted a randomized prospective crossover trial. Nineteen adults with obesity and type 2 diabetes underwent paired 3-h meal tolerance tests (MTT) in randomized order 1-4 weeks apart. Subjects ingested a single dose of DRN and the same nutrients as unformulated powders (UN). RESULTS For DRN compared with UN, the maximal concentration (Cmax) was significantly lower for glucose, c-peptide, and insulin, and the time of maximal concentration (Tmax) was significantly delayed. While Tmax for GLP-1 was also significantly delayed following DRN compared with UN (45 min later; p = 0.26), Cmax did not differ significantly. GLP-1 rose significantly during the last 90 min of the 3-h MTT (β1 = 0.16 pg/mL/min, p = 0.025), while following UN it decreased (β1 = -0.21 pg/mL/min, p = 0.0026) (p difference = 0.0003). There were minimal differences in seven measures of appetite and adverse symptoms between DRN and UN. CONCLUSIONS We conclude that nutrient can be formulated using all-natural ingredients to induce a delayed rise in GLP-1. Further testing is needed to determine the amount and site of nutrient release, when maximum GLP-1 levels occur, and if modification of the formulation specifications and dose are associated with appetite and glucose control.
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Racial Variations in Appetite-Related Hormones, Appetite, and Laboratory-Based Energy Intake from the E-MECHANIC Randomized Clinical Trial.
Dorling, JL, Church, TS, Myers, CA, Höchsmann, C, White, UA, Hsia, DS, Martin, CK, Apolzan, JW
Nutrients. 2019;(9)
Abstract
African Americans (AAs) have a higher obesity risk than Whites; however, it is unclear if appetite-related hormones and food intake are implicated. We examined differences in appetite-related hormones, appetite, and food intake between AAs (n = 53) and Whites (n = 111) with overweight or obesity. Participants were randomized into a control group or into supervised, controlled exercise groups at 8 kcal/kg of body weight/week (KKW) or 20 KKW. Participants consumed lunch and dinner at baseline and follow-up, with appetite and hormones measured before and after meals (except leptin). At baseline, AAs had lower peptide YY (PYY; p < 0.01) and a blunted elevation in PYY after lunch (p = 0.01), as well as lower ghrelin (p = 0.02) and higher leptin (p < 0.01) compared to Whites. Despite desire to eat being lower and satisfaction being higher in AAs relative to Whites (p ≤ 0.03), no racial differences in food intake were observed. Compared to Whites, leptin increased in the 8 KKW group in AAs (p = 0.01), yet no other race-by-group interactions were evident. Differences in appetite-related hormones between AAs and Whites exist; however, their influence on racial disparities in appetite, food intake, and obesity within this trial was limited.