Association between progranulin serum levels and dietary intake.

INTRODUCTION: Progranulin (PGRN) is secreted by adipose tissue and has been linked to obesity, insulin resistance and type 2 diabetes mellitus. There is evidence that a high fat diet increases PGRN expression in rodent adipose tissue. In humans, the relationship between diet composition and concentration of PGRN is still unknown. OBJECTIVE: To investigate the association between dietary intake and serum PGRN levels. METHODS: This is an exploratory cross-sectional study including 85 subjects. Demographic, clinical, laboratory and anthropometric data were collected. Serum PGRN was determined by enzyme-linked immunosorbent assay after overnight fasting. Dietary intake was assessed by food frequency questionnaire validated for Brazilian southern population. Focused principal component analyses (FPCA) was used to verify the association of dietary components and food groups with PGRN levels. Sensitivity analyses were performed including only subjects with reporting according to the Goldberg and Black cut-offs of energy intake-energy expenditure ratio between 0.76 and 1.24. RESULTS: The median PGRN was 51.96 (42.18 to 68.30) ng/mL. Analyzing all sample, the FPCA showed no association of serum PGRN with total energy, protein, carbohydrate, fat and its types, fiber intake and dietary glycemic index; but a significant and positive association between solid fats and PGRN levels (p<0.05). Including only subjects with reporting according cut-off of energy intake-energy expenditure ratio between 0.76 and 1.24, FCPA showed significant and positive association of serum PGRN with saturated fatty acids and solid fats intake (p<0.05). In this subgroup, PGRN correlated with saturated fatty acids (r = 0.341; p = 0.031). Solid fats intake was independently associated to serum PGRN (beta = 0.294; p = 0.004) in multivariate model. CONCLUSION: The dietary intake of solid fats, mainly represented by saturated fatty acids, is associated to serum PGRN concentration in human subjects.

Progranulin serum levels in human kidney transplant recipients: A longitudinal study.

BACKGROUND: The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. OBJECTIVE: To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. METHODS: Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays. RESULTS: Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; p<0.01) and increased at one year (53.15 ± 2.55 ng/mL; p<0.01 vs. three months), remaining significantly lower than before transplantation (p<0.01) (pover time<0.01). At one year after transplantation, there was a significant increase in body mass index, trunk fat and waist circumference compared to immediate period after transplantation. Progranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin. CONCLUSION: Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation.

Serum and Urinary Progranulin in Diabetic Kidney Disease.

Progranulin has been recognized as an adipokine related to obesity, insulin resistance and type 2 diabetes mellitus (T2DM). There are scarce data regarding progranulin and kidney disease, but there are some data linking diabetic kidney disease (DKD) and increased progranulin levels. We aimed to better describe the relationship between serum and urinary progranulin levels and DKD in T2DM. This is a case-control study including four groups of subjects: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2; 2) Albuminuric DKD cases: T2DM patients with urinary albumin excretion (UAE) ≥30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; 3) Diabetic controls: T2DM patients with UAE <30 mg/g creatinine and eGFR ≥60 mL/min/1.73m2; and 4) Non-diabetic controls: individuals without T2DM. Progranulin was determined by enzyme-linked immunosorbent assay. One hundred and fourteen patients were included (23 advanced DKD cases, 25 albuminuric DKD cases, 40 diabetic controls and 26 non-diabetic controls). Serum progranulin was increased in advanced DKD compared to other groups [70.84 (59.04-83.16) vs. albuminuric cases 57.16 (42.24-67.38), diabetic controls 57.28 (42.08-70.47) and non-diabetic controls 44.54 (41.44-53.32) ng/mL; p<0.001]. Urinary progranulin was decreased in advanced DKD cases compared to albuminuric cases [10.62 (6.30-16.08) vs. 20.94 (12.35-30.22); diabetic controls 14.06 (9.88-20.82) and non-diabetic controls 13.51 (7.94-24.36) ng/mL; p = 0.017]. There was a positive correlation between serum progranulin and body mass index (r = 0.27; p = 0.004), waist circumference (r = 0.25; p = 0.007); body fat percentage (r = 0.20; p = 0.042), high-sensitive C reactive protein (r = 0.35; p<0.001) and interleukin-6 (r = 0.37; p<0.001) and a negative correlation with eGFR (r = -0.22; p = 0.023). Urinary progranulin was positively associated with albuminuria (r = 0.25; p = 0.010). In conclusion, progranulin is affected by a decrease in eGFR, being at a higher concentration in serum and lower in urine of DKD patients with T2DM and eGFR <60 mL/min/1.73m2. It is also associated with markers of obesity and inflammation.