Abstract
In order to better understand the link between obesity and type 2 diabetes, lipolysis and its adrenergic regulation was investigated in various adipose depots of obese adult females SHR/N-cp rats. Serum insulin, glucose, free fatty acids (FFA), triglycerides (TG) and glycerol were measured. Adipocytes were isolated from subcutaneous (SC), parametrial (PM) and retroperitoneal (RP) fat pads. Total cell number and size, basal lipolysis or stimulated by norepinephrine (NE) and BRL 37344 were measured in each depot. Obese rats were hyperinsulinemic and hyperglycemic, suggesting high insulin resistance. They presented a marked dyslipidemia, attested by increased serum FFA and TG levels. High serum glycerol levels also suggest a strong lipolytic rate. Obese rats showed an excessive development of all fat pads although a more pronounced effect was observed in the SC one. The cellularity of this depot was increased 8 fold when compared to lean rats, but these fat cells were only 1.5 to 2-fold larger. SC adipocytes showed a marked increase in their basal lipolytic activity but a lack of change in responsiveness to NE or BRL 37344. The association between high basal lipolysis and increased cellularity yields to a marked adipose cell lipolytic rate, especially from the SC region. SHR/N-cp rats were characterized by a hyperplasic type of obesity with an excessive development of the SC depot. The dyslipidemia, attested by an altered serum lipid profile could be attributed to excessive lipolysis that contributes to increased FFA levels, and to early development of insulin resistance through a lipotoxicity effect.
Resumen
La rata SHR/N-cp es un modelo genético que presenta obesidad y diabetes de tipo 2. A fin de comprender mejor el vínculo entre la obesidad y la diabetes, se investiga la lipólisis y su regulación adrenérgica en diversos depósitos adiposos de ratas hembras adultas obesas SHR/N-cp. Se midieron los niveles séricos de insulina, glucosa, ácidos grasos libres, triglicéridos y glicerol. Se utilizaron tres depósitos grasos, subeutáneo (SC), parametrial (PM) y retroperitoneal (RP), que se incubaron con colagenasa para obtener adipocitos aislados. Se determinó el número total de células y su tamanõ. Finalmente, se midió la lipólisis basal y la estimulada para noradrenalina y BRL 37344. El análisis de los parámetros biológicos confirmó que las ratas obesas eran hiperinsulinémicas e hiperglucémicas, lo que sugiere un alto grado de resistencia a la insulina. También presentaron una marcada dislipidemia, con elevados niveles de FFA y de TG. Los altos niveles de glicerol circulante sugieren una elevada tasa lipolítica en los depósitos. Las ratas obesas mostraron un excesivo desarrollo de todos los depósitos grasos, con un efecto más pronunciado en el SC. El número total de células de este depósito fue 8 veces mayor, pero el tamaño de los adipocitos fue sólo 1,5–2 veces superior. Los adipocitos SC mostraron un marcado aumento de su actividad lipolítica basal, pero ésta no cambió en respuesta a NE y BRL 37344. La asociación entre una elevada lipólisis basal y un aumento del número de células adiposas conllevó una mayor tasa lipolítica, especialmente SC. Las ratas SHR/N-cp se caracterizan por una obesidad de tipo hiperplásico, más pronunciada en el depósito subcutáneo. La marcada dislipidemia puede ser atribuida a una excesiva tasa lipolítica que contribuye a un incremento de los FFA circulantes, y, por tanto, a un desarrollo temprano de la resistencia a la insulina a través de un efecto lipotóxico.
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Atgié, C., Hadi-Sassi, A., Bukowiecki, L. et al. High lipolytic activity and dyslipidemia in a Spontaneous Hypertensive/NIH Corpulent (SHR/N-cp) rat: a genetic model of obesity and type 2 diabetes mellitus. J. Physiol. Biochem. 65, 33–41 (2009). https://doi.org/10.1007/BF03165967
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DOI: https://doi.org/10.1007/BF03165967