Association between Nitrogen Stable Isotope Ratios in Human Hair and Serum Levels of Leptin

Abstract

Stable isotope ratios have been reported to be potential biomarkers of dietary intake and nutritional status. High serum levels of leptin, a hormone which regulates energy metabolism and food intake, are associated with insulin resistance and metabolic syndrome. However, little is known about the association between stable isotope ratios and the metabolic risk in humans. We investigated whether the carbon and nitrogen stable isotope ratios in hair are associated with serum leptin levels. Hair samples were collected from 399 healthy adults (233 men and 166 women) aged 40 to 70 years of a community-based cohort in Korea and the bulk stable isotope ratios of carbon (δ 13 C) and nitrogen (δ 15 N) were measured for all hair samples. Serum leptin levels were analyzed by radioimmunoassay. δ 15 N showed positive correlations with serum leptin levels. In multivariate models, increasing δ 15 N were associated with elevated serum leptin levels (defined as ≥ the median values), whereas δ 13 C were not significantly associated with serum leptin levels. The odds ratio (95% confidence interval) per 1‰ increase in δ 15 N for an elevated serum leptin level was 1.58 (1.11-2.26). In participants with high body mass index, δ 15 N showed positive associations with serum leptin levels, whereas these associations were not seen in participants with low body mass index. The nitrogen stable isotopic ratio in hair is positively associated with serum leptin levels. The hair δ 15 N could be used as a clinical marker to estimate metabolic risk.

Stable Isotope Abundance and Fractionation in Human Diseases

“…In a comparison of diabetic patients with controls, no change in hair δ 15 N was found while the δ 13 C value declined and a relationship was found with haemoglobin A1 glycation (HbA1c), this relationship being mostly visible in males [15]. However, in another cohort, hair δ 15 N correlated to plasmatic leptin concentration (in particular in individuals with high body mass index) but no relationship was found with δ 13 C values [16]. In adolescents or children, the δ 13 C value in fingerstick blood samples or in erythrocytes has been found to increase at high food intake (increased sugar intake or high calory diet) and this seemed to be unrelated to HbA1c or to C 4 sugar consumption [17,40].…”

“…Aa metabolism 13 C, 15 N Collagen [12] Chronic malnutrition and potential growth retardation (stunted children) Aa metabolism 13 C, 15 N Hair [13] Patients with metabolic syndrome Glycaemia Aa metabolism 13 C, 15 N Hair [14] Diabetic patients Sugar metabolism 13 C, 15 N Hair [15][16][17][18]…”

“…First, there is an oxygen isotope fractionation as inhaled dioxygen (O 2 ) diffuses through alveolar membranes to pulmonary capillaries. During this process, the rate of 16 O 2 diffusion is about 3‰ larger than that of 16 O- 18 O and furthermore, there is an equilibrium isotope effect during O 2 binding to haemoglobin, leading to an 18 O-depletion in oxygen carried by the vascular system [33]. Second, a fractionation occurs once O 2 is consumed by cellular respiration and converted to water (H 2 O), since mitochondria utilise 16 O 2 about 13‰ faster than 16 O- 18 O [33].…”

“…During this process, the rate of 16 O 2 diffusion is about 3‰ larger than that of 16 O- 18 O and furthermore, there is an equilibrium isotope effect during O 2 binding to haemoglobin, leading to an 18 O-depletion in oxygen carried by the vascular system [33]. Second, a fractionation occurs once O 2 is consumed by cellular respiration and converted to water (H 2 O), since mitochondria utilise 16 O 2 about 13‰ faster than 16 O- 18 O [33]. Given the pathophysiology of anaemias, three potential causes can explain low δ 18 O values.…”

The association between carbon and nitrogen stable isotope ratios of human hair and hypertension

“…Although diet is a significant risk factor for hypertension and metabolic diseases [ 6 , 15 , 16 ], little is known regarding the relationship between stable isotope ratios and metabolic risk in humans. Results of recent studies have suggested the possible association of nitrogen stable isotope ratios with metabolic syndrome and serum leptin levels [ 17 , 18 ].…”