It must be borne in mind that the liver lipid metabolism in MSG rats is clearly displaced to enhanced lipogenesis; thus it could be speculated that, in the postprandial condition any further liver entry of hexoses, through FK downstream reactions, could result in dramatic local lipid overproduction because carbons enter through this pathway bypass glycolysis regulatory steps and are then used in the lipogenic process in a direct and an uncontrolled fashion [45-47].
Indeed, MSG rats displayed several features characteristic of the human Cushing's and metabolic syndrome phenotypes, including a decreased liver weight, high tissue inflammation, and local metabolism highly displaced to an increase in lipid production.
Caption: Figure 4: Liver FK activity (panel (a)), mRNA levels of Srebp1c (panel (b)), Fas (panel (c)), and Gpat (panel (d)) in control (white bars) and MSG rats (black bars).
Table 2: Body weight (BW), daily food intake, wet tissue (visceral adipose tissue, VAT, and liver), and mass and peripheral levels of several biomarkers in control (C) and MSG rats.
Interestingly, metformin treatment in MSG rats delayed the enhancement in plasma lipid concentration up to a similar time to that occurring in CTR rats (3 h); however, these rats did not recover their basal TG levels by the end of the test.
Indeed, data from previous studies performed in MSG rats treated with a high daily metformin dose (300-500 mg/Kg BW) [32-34] indicate that the treatment improves glucose metabolism [32-34], blood pressure , and cardiovascular function [31, 32].
The analysis of our animals' phenotypes indicated that, although all MSG rats remained hypophagic, their overall stunted growth (growing curve, low body weight, and large adiposity) was significantly ameliorated by metformin treatment.