Technical Summary

Obesity and its sequelea (e.g. insulin resistance and type 2 diabetes) have reached epidemic proportions aggravated by high fat diets. We have identified that the Src kinase family member Fyn is a nutrient-sensor regulating insulin sensitivity and lipid metabolism via AMPK and its upstream kinase LKB1, in peripheral tissues. This has broadened to investigations that connect the control of energy metabolism and muscle wasting or sarcopenia, which is associated with deregulations of the circadian clock function. The role of Fyn in circadian metabolic regulation in skeletal muscle is therefore currently under investigation.

More recently, we demonstrated that Fyn participates in the pathogenesis of obesity and that Fyn deficiency protects against high fat diet-induced insulin resistance and inflammation despite the development of obesity. In this context, we identified that Fyn is directly involved in adipose tissue differentiation and we are particularly interested in determining the role of Fyn in visceral and subcutaneous adipose tissues functions. We are also exploring the relevance of Fyn kinase activity in the human obese population and investigating Fyn expression levels and isoform specificity in adipose tissues of selected populations.

Lastly, we identified that Fyn is necessary for the integrity of placental function and is potentially involved in intrauterine growth restriction, a pathology associated with lack of nutrient availability. Therefore we are examining how Fyn connects the energy-sensing pathway (LKB1/AMPK/mTOR) with healthy placental fusion.

Selected publications:

1: Gestational diabetic transcriptomic profiling of micro-dissected human trophoblast.

Bari MF, Ngo S, Bastie CC, Sheppard AM, Vatish M.

J Endocrinol. 2016

Feb 11. pii: JOE-15-0424. [Epub ahead of print] PubMed PMID: 26869332.

2: Fyn deficiency promotes a preferential increase in subcutaneous adipose tissue mass and decreased visceral adipose tissue inflammation.

Lee TW, Kwon H, Zong H, Yamada E, Vatish M, Pessin JE, Bastie CC.

Diabetes. 2013 May;62(5):1537-46. PMCID: PMC3636609.

3: Fyn-dependent regulation of energy expenditure and body weight is mediated by tyrosine

phosphorylation of LKB1.

Yamada E, Pessin JE, Kurland IJ, Schwartz GJ, Bastie CC.

Cell Metab. 2010 Feb 3;11(2):113-24. PMCID:PMC2830006.

4: Integrative metabolic regulation of peripheral tissue fatty acid oxidation by the SRC kinase

family member Fyn.

Bastie CC, Zong H, Xu J, Busa B, Judex S, Kurland IJ, Pessin JE.

Cell Metab. 2007 May;5(5):371-81. PMID: 17488639.