Obesogenic versus ketogenic diets in the regulation of the renin-angiotensin system in rat white and brown adipose tissues

Objective: The ketogenic diet (KD) has been reported to reverse metabolic dysfunction in obesity. However, it remains unknown how the KD affects the balance between the classical and counterregulatory renin-angiotensin system (RAS) arms in adipose tissue, which carries important implications for metabolic function in adipocytes. The aim of this study was to compare the effects of the obesogenic diet and the KD on RAS balance in white and brown fat.

Methods: Nine male Wistar rats were fed a standard chow (SC), 11 fed a high-fat sucrose-enriched (HFS) obesogenic diet, and 12 a KD. At the end of the 8-wk feeding period, subcutaneous inguinal (Sc Ing), epididymal (Epid), and interscapular brown adipose tissue (iBAT) fat depots were extracted and subsequently used for the measurement of RAS proteins and MasR gene expression.

Results: In SC-fed rats, the Sc Ing fat displayed the highest levels of angiotensin-converting enzyme (ACE)1, but very low levels of angiotensin II types 1 and 2 receptors (AT₁R and AT₂R) and ACE2. Conversely, the highest levels of ACE2, AT₁R, and AT₂R were found in iBAT. The HFS diet increased AT₁R protein in Sc Ing fat and iBAT, whereas the KD maintained low AT₁R levels in these fat depots. However, in Sc Ing and Epid fat depots, the KD elevated AT₂R levels and significantly reduced Epid ACE1 levels.

Conclusion: Despite fat depot-specific differences in RAS components, the obesogenic diet promoted the classical RAS arm, whereas the KD attenuated it and enhanced the counterregulatory arm.