Phospholipases D1 and D2 Suppress Appetite and Protect against Overweight.
Obesity is a major risk factor predisposing to the development of peripheral insulin resistance and type 2 diabetes (T2D). Elevated food intake and/or decreased energy expenditure promotes body weight gain and acquisition of adipose tissue. Number of studies implicated phospholipase D (PLD) enzymes and their product, phosphatidic acid (PA), in regulation of signaling cascades controlling energy intake, energy dissipation and metabolic homeostasis. However, the impact of PLD enzymes on regulation of metabolism has not been directly determined so far. In this study we utilized mice deficient for two major PLD isoforms, PLD1 and PLD2, to assess the impact of these enzymes on regulation of metabolic homeostasis. We showed that mice lacking PLD1 or PLD2 consume more food than corresponding control animals. Moreover, mice deficient for PLD2, but not PLD1, present reduced energy expenditure. In addition, deletion of either of the PLD enzymes resulted in development of elevated body weight and increased adipose tissue content in aged animals. Consistent with the fact that elevated content of adipose tissue predisposes to the development of hyperlipidemia and insulin resistance, characteristic for the pre-diabetic state, we observed that Pld1-/- and Pld2-/- mice present elevated free fatty acids (FFA) levels and are insulin as well as glucose intolerant. In conclusion, our data suggest that deficiency of PLD1 or PLD2 activity promotes development of overweight and diabetes.
Rudolf Virchow Center for Experimental Biomedicine University of Würzburg, Josef-Schneider-Str. 2, Haus D15, D-97080 Würzburg, Germany.
Jonathan
J
Trujillo Viera
Rudolf Virchow Center for Experimental Biomedicine University of Würzburg, Josef-Schneider-Str. 2, Haus D15, D-97080 Würzburg, Germany.
Rabih
R
El-Merahbi
Rudolf Virchow Center for Experimental Biomedicine University of Würzburg, Josef-Schneider-Str. 2, Haus D15, D-97080 Würzburg, Germany.|Institute of Experimental Biomedicine, University Hospital of Würzburg, Josef-Schneider-Str. 2, Haus D15, D-97080 Würzburg, Germany.
Bernhard
B
Nieswandt
Rudolf Virchow Center for Experimental Biomedicine University of Würzburg, Josef-Schneider-Str. 2, Haus D15, D-97080 Würzburg, Germany.|Institute of Experimental Biomedicine, University Hospital of Würzburg, Josef-Schneider-Str. 2, Haus D15, D-97080 Würzburg, Germany.
David
D
Stegner
Rudolf Virchow Center for Experimental Biomedicine University of Würzburg, Josef-Schneider-Str. 2, Haus D15, D-97080 Würzburg, Germany.
Grzegorz
G
Sumara
D000818:Animals; D001066:Appetite; D004435:Eating; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018149:Glucose Intolerance / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D050177:Overweight / Q000097:blood / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D010739:Phospholipase D / Q000235:genetics* / Q000378:metabolism
D005227:Fatty Acids; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1