Alta actividad lipolítica y dislipidemia en la rata SHR/N-cp: módulo genético de obesidad y diabetes mellitus tipo 2 / 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

ABSTRACT

In order to better understand the link between obesity and type 2 diabetes, lipolysisand its adrenergic regulation was investigated in various adipose depots of obeseadult 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 numberand size, basal lipolysis or stimulated by norepinephrine (NE) and BRL 37344 weremeasured in each depot. Obese rats were hyperinsulinemic and hyperglycemic, suggestinghigh insulin resistance. They presented a marked dyslipidemia, attested byincreased serum FFA and TG levels. High serum glycerol levels also suggest a stronglipolytic rate. Obese rats showed an excessive development of all fat pads although amore pronounced effect was observed in the SC one. The cellularity of this depot wasincreased 8 fold when compared to lean rats, but these fat cells were only 1.5 to2-fold larger. SC adipocytes showed a marked increase in their basal lipolytic activitybut a lack of change in responsiveness to NE or BRL 37344. The associationbetween high basal lipolysis and increased cellularity yields to a marked adipose celllipolytic rate, especially from the SC region. SHR/N-cp rats were characterized bya hyperplasic type of obesity with an excessive development of the SC depot. Thedyslipidemia, attested by an altered serum lipid profile could be attributed to excessivelipolysis that contributes to increased FFA levels, and to early development ofinsulin resistance through a lipotoxicity effect(AU)