Adipose and muscle tissue profile of CD36 transcripts in obese subjects highlights the role of CD36 in fatty acid homeostasis and insulin resistance.
OBJECTIVE
Fatty acid (FA) metabolism is tightly regulated across several tissues and impacts insulin sensitivity. CD36 facilitates cellular FA uptake, and CD36 genetic variants associate with lipid abnormalities and susceptibility to metabolic syndrome. The objective of this study was to gain insight regarding the in vivo metabolic influence of muscle and adipose tissue CD36. For this, we determined the relationships between CD36 alternative transcripts, which can reflect tissue-specific CD36 regulation, and measures of FA metabolism and insulin resistance.


METHODS
The relative abundance of alternative CD36 transcripts in adipose tissue and skeletal muscle from 53 nondiabetic obese subjects was measured and related to insulin sensitivity and FA metabolism assessed by hyperinsulinemic-euglycemic clamps and isotopic tracers for glucose and FA.


RESULTS
Transcript 1C, one of two major transcripts in adipose tissue, that is restricted to adipocytes predicted systemic and tissue (adipose, liver, and muscle) insulin sensitivity, suggesting adipocyte CD36 protects against insulin resistance. Transcripts 1B and 1A, the major transcripts in skeletal muscle, correlated with FA disposal rate and triglyceride clearance, supporting importance of muscle CD36 in clearance of circulating FA. Additionally, the common CD36 single nucleotide polymorphism rs1761667 selectively influenced CD36 transcripts and exacerbated insulin resistance of glucose disposal by muscle.


CONCLUSIONS
Alternative CD36 transcripts differentially influence tissue CD36 and consequently FA homeostasis and insulin sensitivity. Adipocyte CD36 appears to be metabolically protective, and its selective upregulation might have therapeutic potential in insulin resistance.
Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO.
Terri A
TA
Pietka
Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO.
Timothy
T
Schappe
Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO.
Caterina
C
Conte
Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO.
Elisa
E
Fabbrini
Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO.
Bruce W
BW
Patterson
Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO.
Samuel
S
Klein
Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO.
Nada A
NA
Abumrad
Department of Medicine, Center for Human Nutrition, Washington University, St Louis, MO lgregory@wustl.edu.
Latisha
L
Love-Gregory
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D018955:CD36 Antigens / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D018955:CD36 Antigens; D005227:Fatty Acids; D014280:Triglycerides; D005947:Glucose