Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients.
OBJECTIVE
Weight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain.


METHODS
Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and was re-evaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n=73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2).


RESULTS
After a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR≥2.5) compared with only 25% of patients who maintained the weight loss (p=0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance. Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039).


CONCLUSIONS
Circulating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis.
Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; Cancer Epigenetics and Biology Program (PEBC), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain. Electronic address: anabelencrujeiras@hotmail.com.
Ana B
AB
Crujeiras
Dpt. Nutrition, Food Sciences and Physiology, University of Navarra (UNAV), Pamplona, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
M Angeles
MA
Zulet
Dpt. Nutrition, Food Sciences and Physiology, University of Navarra (UNAV), Pamplona, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
Patricia
P
Lopez-Legarrea
Dpt. Nutrition, Food Sciences and Physiology, University of Navarra (UNAV), Pamplona, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
Rocío
R
de la Iglesia
Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
María
M
Pardo
Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
Marcos C
MC
Carreira
Dpt. Nutrition, Food Sciences and Physiology, University of Navarra (UNAV), Pamplona, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
J Alfredo
JA
Martínez
Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain; CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain.
Felipe F
FF
Casanueva
D052242:Adiponectin / Q000097:blood; D000328:Adult; D005260:Female; D005353:Fibronectins / Q000097:blood*; D054439:Ghrelin / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000178:diet therapy / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015431:Weight Loss
D052242:Adiponectin; C577593:FNDC5 protein, human; D005353:Fibronectins; D054439:Ghrelin; D020738:Leptin; D014409:Tumor Necrosis Factor-alpha
FNDC5; Hypocaloric diet; Insulin sensitivity; Weight regain