Proteomics reveals unique plasma signatures in constitutional thinness

Area of Science:

• Proteomics
• Metabolomics
• Human Physiology

Background:

• Understanding the biological basis of weight gain resistance is crucial for metabolic health.
• Constitutionally thin (CT) individuals exhibit inherent resistance to weight gain, a phenomenon not fully understood.
• Investigating the plasma proteome may reveal molecular mechanisms underlying this resistance.

Purpose of the Study:

• To compare the plasma proteome of constitutionally thin (CT) individuals with normal-weight controls.
• To investigate proteomic changes in response to an overfeeding challenge in CT individuals.
• To identify potential biomarkers for weight-gain resistance in CT subjects.

Main Methods:

• Mass spectrometry-based proteomics was employed for untargeted protein relative quantification.
• Blood plasma samples were collected from 63 CT and normal-weight individuals at baseline, during, and after an overfeeding challenge.
• Longitudinal analysis was performed to assess proteomic responses to nutritional intervention.

Main Results:

• At baseline, CT subjects showed limited proteomic specificity but lower C-reactive protein and higher insulin-like growth factor-binding protein 2 levels.
• During and after overfeeding, CT subjects exhibited a more pronounced and significant plasma proteome response, indicating enhanced resilience.
• Ten proteins were differentially regulated in CT subjects only during overfeeding, including altered levels of fatty acid-binding protein and apolipoprotein C-II.

Conclusions:

• This is the first proteomic profiling of a constitutionally thin cohort, revealing distinct plasma proteomes compared to controls.
• The observed molecular differences support a predominantly biological basis for the weight-gain resistance in CT individuals.
• Findings provide insights into weight management strategies and potential diagnostic markers for weight-gain resistant phenotypes.