BACKGROUND/OBJECTIVE: Diet-induced weight loss (WL) leads to increased hunger and reduced fullness feelings, increased ghrelin and reduced satiety peptides concentration (glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK) and peptide YY (PYY)). Ketogenic diets seem to minimise or supress some of these responses. The aim of this study was to determine the timeline over which changes in appetite occur during progressive WL with a ketogenic very-low-energy diet (VLED). SUBJECTS/METHODS: Thirty-one sedentary adults (18 men), with obesity (body mass index: 37 ± 4.5 kg m − 2 ) underwent 8 weeks (wks) of a VLED followed by 4 wks of weight maintenance. Body weight and composition, subjective feelings of appetite and appetite-related hormones (insulin, active ghrelin (AG), active GLP-1, total PYY and CCK) were measured in fasting and postprandially, at baseline, on day 3 of the diet, 5 and 10% WL, and at wks 9 and 13. Data are shown as mean ± s.d. RESULTS: A significant increase in fasting hunger was observed by day 3 (2 ± 1% WL), (P o 0.01), 5% WL (12 ± 8 days) (P o0.05) and wk 13 (17 ± 2% WL) (P o 0.05). Increased desire to eat was observed by day 3 (P o 0.01) and 5% WL (P o 0.05). Postprandial prospective food consumption was significantly reduced at wk 9 (16 ± 2% WL) (P o 0.01). Basal total PYY was significantly reduced at 10% WL (32 ± 8 days) (P o 0.05). Postprandial active GLP-1 was increased at 5% WL (P o 0.01) and CCK reduced at 5 and 10% WL (P o0.01, for both) and wk 9 (P o 0.001). Basal and postprandial AG were significantly increased at wk 13 (Po 0.001, both). CONCLUSIONS: WL with a ketogenic VLED transiently increases the drive to eat up to 3 weeks (5% WL). After that, and while participants are ketotic, a 10-17% WL is not associated with increased appetite. However, hunger feelings and AG concentrations increase significantly from baseline, once refeeding occurs. INTRODUCTIONObesity has reached epidemic proportions worldwide and is associated with negative public health consequences and large socioeconomic costs. 1 A weight loss (WL) between 5 and 10% of baseline weight, if sustained, can have large health benefits by preventing or improving several obesity-related risk factors and comorbidities. 2 Even though this can be achieved in the shortterm with lifestyle interventions, 3 most adults will experience weight regain in the long term. [3][4][5] Maintaining lost weight is physiologically challenging, as dietinduced WL is associated with compensatory responses on both sides of the energy balance equation. 6 These responses are driven by a cross talk between the gut and the brain, leading to an increase in appetite and reduction in satiety, 7-9 concomitant with an overall reduction in energy expenditure. [10][11][12] These mechanisms can reduce WL rate and increases the risk of relapse. 9 An increase in ghrelin plasma concentration [13][14][15] and a reduction in the concentration of several satiety hormones, such as peptide YY (PYY), glucagon-like peptide-1 (GLP-1) 13,[16][17][18] and cholecystokinin (...

Background/ObjectiveDiet-induced weight loss (WL) leads to a compensatory increase in appetite and changes in the plasma concentration of appetite-regulating hormones are likely to play a role. Whether these changes are transient or sustained remains unclear. This study aimed to assess if changes in subjective and objective appetite markers observed with WL are sustained after 1 year (1Y).Subjects/MethodsIn total 100 (45 males) individuals with obesity (BMI: 37 ± 4 kg/m2, age: 43 ± 10 years) underwent 8 weeks (wks) of a very-low energy diet (VLED), followed by 4 wks refeeding, and a 1Y maintenance program. Fasting/postprandial subjective ratings of hunger, fullness, desire to eat, and prospective food consumption (PFC) were assessed, and plasma concentration of active ghrelin (AG), total peptide YY (PYY), active glucagon-like peptide 1, cholecystokinin (CCK), and insulin measured, at baseline, week 13 (Wk13) and 1Y.ResultsAt Wk13, 16% WL (−18 ± 1 kg, P < 0.001) was associated with a significant increase in fasting and postprandial hunger ratings (P < 0.01 and P < 0.05, respectively), and postprandial fullness (P < 0.01) combined with a reduction in PFC (P < 0.001). These were accompanied by a significant rise in basal and postprandial AG concentrations (P < 0.001, for both), a reduction in postprandial CCK (P < 0.01) and in basal and postprandial insulin (P < 0.001). At 1Y follow-up, with sustained WL (15%; −16 ± 1 kg, P < 0.001), fasting hunger and postprandial fullness ratings remained increased (P < 0.05 for both), and postprandial PFC reduced (P < 0.001). Basal and postprandial AG remained elevated and insulin reduced (P < 0.001, for all), while postprandial CCK was increased (P < 0.01) and PYY decreased (P < 0.001).ConclusionWith a 15% sustained WL at 1Y, the drive to eat in the fasting state is increased, but this may be balanced out by raised postprandial feelings of fullness. To assist with WL maintenance, new strategies are required to manage increased hunger and drive to eat.

Objective To compare appetite markers in reduced-obese individuals with a nonobese control group. Methods A total of 34 adults with obesity who lost 17% body weight at week 13 and maintained this weight loss (WL) at 1 year were compared with 33 nonobese controls matched for body composition. Basal and postprandial subjective appetite ratings and appetite-related hormone concentrations (ghrelin, total peptide YY, peptide YY3-36, total and active glucagon-like peptide 1, and cholecystokinin) were measured in all participants and repeated at week 13 and 1 year in the weight-reduced group. Results WL led to a reduction in prospective food consumption and an increase in feelings of hunger, fullness, and ghrelin secretion (basal and postprandial), but these new ratings were no different from those seen in controls. Postprandial concentrations of active glucagon-like peptide 1, total peptide YY, and cholecystokinin were lower in individuals with obesity at all time points compared with controls. Conclusion The increased drive to eat (both subjective feelings of hunger and ghrelin concentrations) seen in reduced-obese individuals, both after acute and sustained WL, reflects a normalization toward a lower body weight. Overall, WL does not have a sustained negative impact on satiety peptide secretion, despite a blunted secretion in individuals with obesity compared with nonobese controls.

Diet-induced weight loss (WL) is associated with reduced resting and non-resting energy expenditure (EE), driven not only by changes in body composition but also potentially by adaptive thermogenesis (AT). When exactly this happens, during progressive WL, remains unknown. The aim of this study was to determine the timeline of changes in RMR and exercise-induced EE (EIEE), stemming from changes in body composition v. the presence of AT, during WL with a very-low-energy diet (VLED). In all, thirty-one adults (eighteen men) with obesity (BMI: 37 (sem 4·5) kg/m2; age: 43 (sem 10) years) underwent 8 weeks of a VLED, followed by 4 weeks of weight maintenance. Body weight and composition, RMR, net EIEE (10, 25 and 50 W) and AT (for RMR (ATRMR) and EIEE (ATEIEE)) were measured at baseline, day 3 (2 (sem 1) % WL), after 5 and 10 % WL and at weeks 9 (16 (sem 2) %) and 13 (16 (sem 1) %). RMR and fat mass were significantly reduced for the first time at 5 % WL (12 (sem 8) d) (P<0·01 and P<0·001, respectively) and EIEE at 10 % WL (32 (sem 8) d), for all levels of power (P<0·05), and sustained up to week 13. ATRMR was transiently present at 10 % WL (−460 (sem 690) kJ/d, P<0·01). A fall in RMR should be anticipated at ≥5 % WL and a reduction in EIEE at ≥10 % WL. Transient ATRMR can be expected at 10 % WL. These physiological adaptations may make progressive WL difficult and will probably contribute to relapse.