Six months after gastric bypass, the gut peptide PYY correlated positively with the brain appetite-suppressing peptide α-MSH (r=0.35, p=0.004) while correlating negatively with BMI, supporting the PYY-POMC signaling axis in post-surgical appetite regulation.
PYY-αMSH correlation: r=0.35, p=0.004Six months after gastric bypass, the gut peptide PYY and brain appetite-suppressor α-MSH were significantly correlated, while PYY inversely correlated with BMI
What the researchers found
In 39 individuals with extreme obesity, 6 months after Roux-en-Y gastric bypass:
- BMI decreased from 44.3 ± 6.4 to 31.7 ± 5.7 kg/m² (P < 0.001)
- Percentage of excess weight lost: 63.2 ± 25.0%
- Leptin and glucose levels decreased significantly (P < 0.001)
- Significant positive correlation between PYY and α-MSH after surgery (r = 0.35, P = 0.004)
- PYY correlated negatively with BMI (r = -0.34, P = 0.002)
- Supports the PYY-to-POMC signal as a mechanism for appetite regulation post-RYGB
Why it matters
Understanding why gastric bypass works so well for weight loss — better than any drug — can help develop new medications. This study reveals a gut-brain peptide connection (PYY → α-MSH/POMC) that may be a key mechanism. If this pathway can be pharmacologically activated without surgery, it could lead to more effective obesity treatments.
How the study worked
Prospective observational study of 39 individuals with extreme obesity (37 women, 2 men) undergoing Roux-en-Y gastric bypass. Anthropometric measurements and biochemical markers (including PYY, α-MSH, leptin, glucose) were collected before surgery and 6 months post-RYGB. Correlations between hormone levels and BMI changes were analyzed.
What this study cannot tell us
Small sample size (39 patients) with predominantly female participants (37/39), limiting generalizability to men. The observational design cannot establish causation. PYY and α-MSH were measured at only two time points. The study did not measure GLP-1 or other gut peptides that likely also contribute to post-surgical appetite suppression. Six-month follow-up may not reflect long-term hormonal changes.
How to read the evidence
This is a small, single-arm observational study without a control group. While it reveals interesting hormone correlations, the design cannot prove that the PYY-α-MSH relationship causes the weight loss or appetite suppression.
When this study was published
Published in 2016, this study provides early human evidence for the PYY-POMC appetite signaling axis after gastric bypass, a concept that continues to inform obesity drug development.
The bigger picture
PYY and α-MSH are both targets of current obesity drug development. PYY reduces appetite through Y2 receptors and POMC neuron activation, while α-MSH (from POMC) directly suppresses appetite through MC4 receptors. This study provides human evidence that gastric bypass enhances this peptide signaling cascade, helping explain why surgery is more effective than diet alone. GLP-1 drugs partially mimic this gut-brain signaling.
Questions still open
- Could drugs that simultaneously boost PYY and activate the POMC/α-MSH pathway replicate gastric bypass's appetite suppression?
- How does the PYY-α-MSH correlation change in the years after gastric bypass as some patients experience weight regain?
- Do GLP-1 drugs also enhance the PYY-POMC signaling axis, and could this explain their effectiveness?
Common questions
How does gastric bypass change appetite-controlling peptides?
What is the PYY-POMC signaling pathway?
Read the original research
Early effects of Roux-en-Y gastric bypass on peptides and hormones involved in the control of energy balance.
European journal of gastroenterology & hepatology, 28(9), 1050-5
Citation
Molin Netto, Bárbara Dal; Earthman, Carrie P; Cravo Bettini, Solange; Grotti Clemente, Ana Paula; Landi Masquio, Deborah Cristina; Farias, Gisele; Boritza, Katia; da Silva, Larissa Gabrielle; von der Heyde, Maria Emilia; Dâmaso, Ana Raimunda. (2016). Early effects of Roux-en-Y gastric bypass on peptides and hormones involved in the control of energy balance.. European journal of gastroenterology & hepatology, 28(9), 1050-5. https://doi.org/10.1097/MEG.0000000000000665