Changes in adipocytokines and myokine expression during weight loss in subjects with obesity

Van de Velde Frederique; Ouwens Margriet; Batens Arsene-Helene; Van Nieuwenhove Yves; Lapauw Bruno

doi:10.1530/endoabs.71.023

Background and aim: Adipose and muscle tissue dysfunction are associated with obesity-related complications, especially insulin resistance (IR) and inflammation, which improve after weight loss. The underlying mechanisms are however not yet fully understood. This study investigates changes in systemic and regional markers of IR and inflammation during weight loss in subjects with obesity.

Materials and methods: Twenty subjects with obesity (age 49±10 years, 14 men) were recruited prior to gastric bypass surgery. On baseline, and six months and one year thereafter, subcutaneous abdominal adipose tissue (SAT), skeletal muscle and fasting serum samples were collected. Sixteen subjects had biopsies in follow-up. Serum levels of C-reactive protein (CRP), glucose and insulin were determined using standard laboratory assays and interleukin-6 (IL-6), interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α) using ELISA. HOMA-IR was calculated. mRNA expression in adipose and muscle tissue of glucose transporter 4 (GLUT4), bone morphogenetic protein 4 (BMP4), IL6, IL10, monocyte chemoattractant protein 1 (MCP1), insulin receptor substrate 1 (IRS1) and TNFα was determined using qPCR.

Results: During weight loss, BMI decreased along with systemic improvement in inflammation (CRP and IL-6 levels) and IR (see table). Serum IL-10 and TNF-α levels did not change (P>0.05). In muscle tissue, mRNA expression of BMP4, GLUT4 and IL-6 decreased and MCP1 and IRS1 increased. In SAT, mRNA expression of BMP4, IL-6, IL-10 and MCP1 decreased and GLUT4 increased (see table). IL-10 expression, only in muscle tissue, and TNF-α expression, in both tissues, remained unchanged (all P>0.05).

	Baseline	6 months	1 year
BMI (kg/m²)	43.6±4.7	32.3±4.2**	29.8±3.5**
Serum CRP (nmol/)	41.9 (21.9–80.95)	14.29 (8.57–26.67)**	8.57 (8.57–19.05)**
HOMA-IR	6.41 (4.64–7.62)	1.12 (0.84–1.42)**	0.92 (0.72–1.39)**
Serum IL6 (pg/ml)	2.70 (2.29–4.51)	2.15 (1.73–4.39)	1.43 (1.09–2.60)*
Muscle BMP4°	12.0 (8.8–14.3)	7.7 (6.7–8.4)*	9.6 (6.6–11.0)*
Muscle GLUT4°	833.1 (740.6–957.9)	676.6 (653.6–718.6)*	860.2 (735.7–909.9)
Muscle IL6°	1.5 (0.9–2.4)	0.4 (0.3–0.5)**	0.3 (0.2–0.4)**
Muscle MCP1°	3.3 (2.4–4.9)	7.2 (6.3–9.4)**	10.1 (8.9–12.1)**
Muscle IRS1°	155.2 (125.6–233.7)	215.6 (167.0–272.0)*	198.3 (193.3–274.3)*
SAT BMP4°	246.8 (200.6–338.5)	147.5 (127.4–216.3)*	188.8 (167.2–205.1)
SAT GLUT4°	4443 (3915–5578)	5876 (5078–7018)**	5405 (5000–6296)*
SAT IL6°	2953 (1580–4531)	64.8 (31.8–85.4)**	56.1 (31.6–72.1)**
SAT IL10°	200.6 (95.8-276.2)	77.1 (49.4–129.0)*	35.2 (32.0–64.8)**
SAT MCP1°	6069 (3052–8433)	1519 (1082–2203)*	1172 (1057–1310)*
Data presented as median (25%–75%). mRNA expression expressed as fold change with reference to household genes ((10^–3). Bold numbers indicate significant differences from baseline (P<0.05 and *P<0.001).

Conclusion: Systemic improvements in inflammation and IR after GBS are mirrored by changes in tissue expression of inflammatory adipocytokines and myokines during weight loss in a population with obesity. Further research needs to clarify whether addressing these inflammatory pathways in obesity might help prevent or mitigate obesity-related complications.

Endocrine Abstracts

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