Acute Caloric Restriction Improves Adipokine Profile with Concomitant Increase in Glucose Reabsorption and Decreased Gluconeogenesis in Obese, Insulin‐Resistant Rats
Authors: Cornejo Manuel Alejandro , Nguyen Julie , Cazares Joshua , Escobedo Benny , Nishiyama Akira , Nakano Daisuke , Ortiz Rudy Martin 
Published: June 2021

The adipokine leptin has an important role in regulating body mass, and high concentrations lead to a resistance in target organs (e.g. β‐cells). Adiponectin, on the other hand, is considered antidiabetic and is inversely correlated to adipose tissue mass, which is reduced via caloric restriction (CR). SGLT2 transporter expression in the kidney is increased in diabetic conditions, leading to a higher glucose reabsorption and maintained hyperglycemia. During conditions of caloric restriction, increased hepatic PEPCK‐C expression contributes to an increase in hepatic gluconeogenesis via production of G3P. Our goal was to assess the effect of acute CR on adipokine profile and glucose metabolism in an obese, insulin resistant, animal model.

Twenty‐eight lean LETO and 28 obese, insulin resistant OLETF rats were separated in two ad libidum food control groups (n=14 each), two CR groups, and two partial recovery (PR) groups (n=7 each). All groups were fed ad libidum for 4 weeks. After that time CR and PR groups were fed half the mean food intake of the ad libidum LETO group for 10 days, after which CR were dissected. The PR groups were fed ad libidum for 7 days and dissected.

Blood was collected during dissection after 12 h fasting, and serum was preserved for measuring adipokines. Both leptin and adiponectin were measured by commercially available ELISA kits. SGLT2 and PEPCK‐C expression were measured by Western Blot from the kidney cortex and liver, using Ponceau stain as a loading control.

Mean serum leptin was higher in OLETF (P=0.038) than LETO, but decreased 3‐fold after CR and recovered below threshold levels after PR (8.6 ± 1.2 in PR vs 15.4 ± 4.5 ng/ml Control). Serum adiponectin remained unchanged in both strains after CR, but increased after PR (2.3 ± 0.2 To 3.7 ± 0.2, P<0.001 in LETO and 3.3 ± 0.2 to 3.9 ± 0.1 μg/ml, P=0.05 in OLETF). Baseline leptin‐adiponectin ratio was 3‐fold higher in OLETF vs LETO. However, the ratio decreased 2‐fold in LETO and 3‐fold in OLETF (P<0.001) after CR (Fig. 1)

Mean SGLT2 expression in the kidney increased after CR in both strains (21%, in LETO and 40%, in OLETF), and that increase was maintained in OLETF, but not for LETO, after PR (Fig. 2). Changes in PEPCK‐C expression in LETO were not detectable; however, expression in OLETF was higher than LETO (P<0.001) and decreased after CR (222% to 178%) and even further after PR (to 124%) (Fig. 3). Nonetheless, mean expression for PR control in OLETF is half of CR control, suggesting a high variability within the strain.

In conclusion, an acute caloric restriction improves adipokine profile in both strains even after PR, suggesting a protective effect by increased expression of adiponectin with reduced fat mass. Moreover, glucose reabsorption in the kidney may be enhanced in lieu of increased gluconeogenesis and contributing to the hyperglycemia associated with the development of T2D.

Support or Funding Information

This research was funded by a doctoral fellowship from UC MEXUS‐CONACYT and an MHIRT Fellowship.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.