Changes in 25(OH) vitamin D levels, leptin levels and visceral adipose tissue volume: Results from a lifestyle intervention program in viscerally obese men.

Anne Gangloff1,2,3 (MD, PhD), Jean Bergeron2 (MD, MSc) Isabelle Lemieux1 (PhD), Angelo Tremblay1 (PhD), Paul Poirier1 (MD, PhD), Natalie Alméras1 (PhD), Jean-Pierre Després1

(PhD) 1 Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec City, Québec, Canada.

2 Lipid Research Centre, Service of Lipidology, Department of Medicine, Université Laval, Centre Hospitalier Universitaire de Québec, Pavilion CHUL, Québec City, Québec, Canada. 3 Endocrinology and Nephrology Unit, CHU de Québec Research Centre, 2705 Boulevard Laurier, Québec City, Canada.

Abstract

Background/synopsis: Vitamin D deficiency and elevated leptinemia have both been associated with obesity in numerous studies. To date, whether there is an association between vitamin D and leptin levels independent from adiposity remains uncertain. Purpose: To investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables and changes in leptin levels following a 1-year lifestyle intervention program. Methods: Design and Setting: Intervention study (SYNERGIE study) performed on participants recruited from the general community. Participants: Sedentary, abdominally obese and dyslipidemic men (n=113) involved in a 1-year lifestyle modification program. Intervention: Subjects were individually counselled by a kinesiologist and a nutritionist once every 2 weeks during the first 4 months with subsequent monthly visits in order to elicit a 500 kcal daily energy deficit and to increase physical activity/exercise habits. Main Outcome Measures: Cardiometabolic risk profile and adiposity mapping by computed tomography, to which a plasma vitamin D measurement was added. Results: The 1-year intervention resulted in a 27% increase in plasma 25(OH) vitamin D (from 50±18 nmol/L to 60±18 nmol/L, p<0.0001), a 26% decrease in visceral adipose tissue volume (from 1951±481 cm3 to 1463±566 cm3) and a 27% decrease in leptin (from 12±8 ng/mL to 9±8 ng/mL). One-year increases in 25(OH)D levels correlated inversely with 1-year changes in leptin levels (r=-0.41, p<0.001). The association remained significant after adjustment for 1-year changes in various adiposity indices: visceral adipose tissue (r=-0.30, p=0.002), subcutaneous adipose tissue (r=-0.35, p=0.0004), total abdominal adipose tissue (r=-0.31, p=0.002) and fat mass (r=-0.31, p=0.001). Conclusions: Changes in 25(OH) vitamin D were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports the notion of a possible link between 25(OH)D vitamin D and leptin independent from adiposity.

Conclusion

Objective

Methods

Acknowledgements

Summary To investigate the associations between changes in 25(OH) vitamin D levels, changes in adiposity variables and changes in leptin levels following a 1-year lifestyle intervention program.

Subjects: 113 men between 30 and 65 years, presenting abdominal obesity (waist circumference ≥90 cm), triglyceride levels ≥1.69 mmol/L and/or HDL-cholesterol <1.03 mmol/L were included in a lifestyle intervention. Subjects with type 2 diabetes, body mass index (BMI) values <25 or >40 kg/m2, taking medication targeting glucose metabolism, lipid metabolism, or blood pressure management were excluded. Intervention: Subjects were individually counselled by a dietician and a kinesiologist once every 2 weeks during the first 4 months of the intervention with subsequent monthly visits. The goal was to reduce calorie consumption by 500 kcal/day during the first year. The physical activity program aimed to reach 160 min/week of moderate intensity endurance exercise. Diet and fitness assessment: A 3-day dietary record both at the initial visit and at the 1-year follow-up was used to quantify overall nutritional quality. A standardized exercise test was performed to assess cardiorespiratory fitness using the subject's heart rate at a standardized submaximal treadmill workload (3.5 mph, 2% slope). Anthropometry, body composition and adiposity mapping: Height, weight, hip circumference and waist circumference were measured according to standardized procedures. Dual-energy X-ray absorptiometry was used to assess fat mass. VAT, subcutaneous adipose tissue (SAT) and total adipose tissue (TAT) cross-sectional areas were assessed by computed tomography and partial volumes between L2–L3 and L4–L5 were calculated. 25(OH) vitamin D measurement: Plasma samples were collected in EDTA vacutainers at the initial and at the 1-year follow-up visits. The Vitamin D Total assay from Roche was used and measurements were performed in batch on a MODULAR ANALYTICS E170 (Roche). Circulating 25(OH)D levels were adjusted for the season of venipuncture. Leptin and adiponectin measurements: Plasma leptin and adiponectin concentrations (B-Bridge, CA) were determined by ELISA on frozen plasma samples (-80°C). Statistical analysis: All statistical analyses were performed using SAS 9.4.

•  Vitamin D [25(OH)D] insufficiency and obesity are two prevalent health conditions worldwide.

•  A high prevalence of 25(OH)D insufficiency has been reported among obese individuals.

•  Cross-sectional studies have already established a negative association between visceral adipose tissue (VAT) volume and circulating 25(OH)D levels. We have recently reported that the reduction in adiposity, especially VAT reduction, produced by a lifestyle modification program was associated with an increase in circulating vitamin D levels (Gangloff A. et al. Int J Obes 2015, 39; 1638-1643).

•  A recent meta-analysis investigating the effects of vitamin D supplementation on adipokine levels indicated that increases in 25(OH)D levels following vitamin D supplementation were significantly associated with decreases in leptin levels. No significant effect of vitamin D supplementation on adiponectin and leptin levels was found (Dinca M. et al. Pharmacol Res 2016, 107; 360-371).

•  To date, no intervention study has investigated whether the relationship between adipose tissue volume loss and increases in circulating 25(OH)D levels in non-vitamin D supplemented men could be mediated, at least in part, by changes in adipokine levels.

Background Results

•  One-year changes in adiposity, 25(OH)D, leptin, adiponectin, steps per day and heart rate at submaximall treadmill workload were all statistically significant and improved between baseline and the 1-year visits (Table 1).

•  Significant associations were found between changes in circulating 25(OH)D levels and changes in volume of every adipose tissue depot (Table 2).

•  One-year changes in adipokine levels (leptin and adiponectin) are associated with 1-year changes in adiposity volume variables (Table 3).

•  One-year changes in 25(OH)D levels were correlated with changes in leptin and adiponectin levels, the association being stronger between 25(OH)D changes and leptin changes (Figures 1 and 2).

•  The relationship between changes in 25(OH)D levels and changes in leptin levels remained significant after adjusting for changes in adipose tissue volume (Table 4).

•  However, the relationship between changes in 25(OH)D and changes in adiponectin levels became nonsignificant after control for changes in adipose tissue volume (Table 4).

Changes in 25(OH) vitamin D were independently associated with changes in leptinemia after adjustment for adiposity changes. This finding supports the notion of a possible link between 25(OH)D vitamin D and leptin independent from adiposity.

This study was supported by the Canadian Institutes of Health Research.

Table 1: Characteristics of the sample of 113 men involved in the 1-year lifestyle intervention program

Table 2: Correlations between 1-year changes in 25(OH)D and 1-year changes in adiposity variables

Table 3: Correlations between 1-year changes in adipokines and 1-year changes in adiposity variables

Figure 1: Correlation between changes in leptinemia and changes in 25(OH) vitamin D levels in response to a 1-year lifestyle modification program

Figure 2: Correlation between changes in adiponectinemia and changes in 25(OH) vitamin D in response to a 1-year lifestyle modification program

Table 4: Partial correlations between 1-year changes in 25(OH)D and 1-year changes in adipokines after adjustment for 1-year changes in adiposity indices

!1#year!changes!in! 1#year!changes!in!25(OH)D!!r!value!

!P!value!

! ! !SAT!volume!! "0.27! 0.0057!VAT!volume! "0.30! 0.0018!TAT!volume! "0.33! 0.0007!Fat!mass! "0.28! 0.0035!BMI! "0.28! 0.0026!Waist!girth! "0.28! 0.0032!!

!1#year!changes!in! 1#year!changes!in!!r!value!

!P!value!

! ! !!! LEPTIN! !!SAT!volume!! 0.49! <0.0001!VAT!volume! 0.48! <0.0001!TAT!volume! 0.51! <0.0001!Fat!mass! 0.55! <0.0001!BMI! 0.55! <0.0001!Waist!girth! 0.49! <0.0001!!! !! !!!! ADIPONECTIN! !!SAT!volume!! #0.40! <0.0001!VAT!volume! #0.30! 0.0023!TAT!volume! #0.35! 0.0004!Fat!mass! #0.38! <0.0001!BMI! #0.34! 0.0003!Waist!girth! #0.36! 0.0002!!

1"year'changes'in' Adjusted'for'1"year'changes'in'

1"year'changes'in'25(OH)D'Partial'r'value'

P'value'

' ' ' 'Leptin' SAT'volume' "0.35' 0.0004'Leptin' VAT'volume' "0.30' 0.0019'Leptin' TAT'volume' "0.31' 0.0015'Leptin' Fat'mass' "0.31' 0.0010''' '' ' ''Adiponectin' SAT'volume' 0.12' NS'Adiponectin' VAT'volume' 0.12' NS'Adiponectin' TAT'volume' 0.12' NS'Adiponectin' Fat'mass' 0.11' NS'!

!! Baseline! Post!1!year!! Absolute!

changes!

%!changes! !P!value!

!!

! ! ! ! ! !

Age!(years)! 48!±9! 49!±9! +1.2!±0.1! +3! <0.0001!

!! !! !! !! ! !!

Anthropometry! !! !! !! ! !!

Weight!(kg)! 95.0!±11.9! 88.2!±12.1! H6.8!±4.6! H7! <0.0001!

BMI!(kg/m2)! 31.1!±3.1! 28.9!±3.3! H2.2!±1.5! H7! <0.0001!

Waist!circumference!(cm)! 108.3!±8.9! 99.9!±10.0! H8.7!±5.4! H8! <0.0001!

!! !! !! !! ! !!

Adiposity! !! !! !! ! !!

SAT!volume!(cm3)! 1781!±639! 1454!±575! H330!±264! H18! <0.0001!

VAT!volume!(cm3)! 1951!±481! 1463!±566! H497!±349! H26! <0.0001!

TAT!volume!(cm3)! 3723!±893! 2900!±936! H832!±560! H23! <0.0001!

Fat!mass!(kg)! 29.5!±7.1! 23.5!±7.7! H6.0!±3.9! H21! <0.0001!

!! !! !! !! ! !!

Hormones! !! !! !! ! !!

25(OH)!vitamin!D!(nmol/L)! 50!±18! 60!±18! +10!±13! +27! <0.0001!

Leptin!(ng/mL)! 12.0!±8.1! 8.5!±7.8! H3.5!±4.1! H27! <0.0001!

Adiponectin!(ug/mL)! 3.8!±1.5! 4.5!±1.8! +0.8!±1.1! +26! <0.0001!

!! !! !! !! ! !!

Lifestyle! !! !! !! ! !!

Daily!caloric!intake!(kcal)! 3033!±627! 2439!±504! H571!±669! H17! <0.0001!

Steps!per!day! 7614!±2810! 9759!±3198! +2022!±2791! +37! <0.0001!

Heart!rate!at!submaximal!

treadmill!workload!

(beats/min)!

118!±14! 104!±14! H13!±11! H11! <0.0001!

!

r=#0.41,)p<0.0001)

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