Moderate weight loss corrected leptin and ghrelin rhythms toward normal patterns, but subjective hunger and fullness feelings did not change.
Hormones changed, appetite didn'tleptin and ghrelin rhythms normalized after weight loss, but hunger and fullness feelings remained unchanged
What the researchers found
Weight loss produced the expected hormonal changes: leptin (the fullness hormone) decreased overall (P = 0.020 for area under curve and mean level). Ghrelin (the hunger hormone) increased. Both hormones' daily rhythms were modified to more closely resemble those of normal-weight individuals.
The amount of variability in leptin and ghrelin daily rhythms correlated with diet effectiveness (P < 0.001 for both). People whose hormone rhythms changed more also lost more weight.
The disconnect: despite these hormonal improvements, subjective appetite sensations (hunger, fullness, desire to eat) barely changed. Patients still felt approximately the same hunger after losing weight as before.
This confirms that in obesity, the hormonal signals (leptin and ghrelin) cannot properly reach or influence the brain centers that control conscious hunger and satiety. Weight loss partially restores the hormones but does not fix the broken communication.
Why it matters
This explains why dieting is so hard. Even when weight loss corrects hormone levels, the brain does not get the message. The hormones are screaming "you're not hungry" but the person still feels hungry. Understanding this hormone-brain disconnect is key to developing better obesity treatments.
The numbers in context
20 obese, 13 controls; 12 weeks; leptin decreased P=0.020; ghrelin increased; rhythm variability correlated with weight loss P<0.001; appetite unchanged
How the study worked
Interventional study with 20 obese subjects and 13 normal-weight controls. Obese participants underwent 12 weeks of calorie-restricted diet. Plasma leptin and ghrelin were measured at baseline and end of intervention with multiple time points to capture daily rhythms. Appetite was assessed using validated visual analog scales.
Who was studied
20 obese adults + 13 normal-weight controls
What this study cannot tell us
Small sample (20 obese, 13 controls). Twelve weeks may not be long enough for appetite regulation to fully adapt. Appetite was measured by self-report, which is subjective. The study measured only leptin and ghrelin; other appetite-regulating hormones (GLP-1, PYY, CCK) were not assessed. No long-term follow-up to see if appetite eventually recalibrates.
How to read the evidence
Preliminary evidence from a small interventional study. Clear hormonal changes documented, but the appetite disconnect needs confirmation in larger, longer studies.
When this study was published
Published in 2020. The hormone-appetite disconnect is now better understood and informs GLP-1 drug development.
The bigger picture
This explains a fundamental challenge in obesity treatment: even when hormones normalize, the brain may not register the change. The disconnect between hormonal signals and conscious appetite suggests that weight management requires addressing both biology and perception.
Questions still open
- How long after weight loss do appetite sensations eventually align with hormones?
- Do GLP-1 drugs succeed because they bypass this hormone-perception disconnect?
- Would longer-duration studies show eventual appetite normalization?
Common questions
If my hormones improve with weight loss, why am I still hungry?
Does this mean dieting is pointless?
Read the original research
Moderate Weight Loss Modifies Leptin and Ghrelin Synthesis Rhythms but Not the Subjective Sensations of Appetite in Obesity Patients.
Nutrients, 12(4)
Citation
Hernández Morante, Juan José; Díaz Soler, Inmaculada; Muñoz, Joaquín S Galindo; Sánchez, Horacio Pérez; Barberá Ortega, Mª Del Carmen; Martínez, Carlos Manuel; Morillas Ruiz, Juana Mª. (2020). Moderate Weight Loss Modifies Leptin and Ghrelin Synthesis Rhythms but Not the Subjective Sensations of Appetite in Obesity Patients.. Nutrients, 12(4). https://doi.org/10.3390/nu12040916