Cafeteria Diet Feeding in Young Rats Leads to Hepatic Steatosis and Increased Gluconeogenesis under Fatty Acids and Glucagon Influence

Abstract

Gluconeogenesis overstimulation due to hepatic insulin resistance is the best-known mechanism behind elevated glycemia in obese subjects with hepatic steatosis. This suggests that glucose production in fatty livers may differ from that of healthy livers, also in response to other gluconeogenic determinant factors, such as the type of substrate and modulators. Thus, the aim of this study was to investigate the effects of these factors on hepatic gluconeogenesis in cafeteria diet-induced obese adult rats submitted to a cafeteria diet at a young age. The livers of the cafeteria group exhibited higher gluconeogenesis rates when glycerol was the substrate, but lower rates were found when lactate and pyruvate were the substrates. Stearate or glucagon caused higher stimulations in gluconeogenesis in cafeteria group livers, irrespective of the gluconeogenic substrates. An increased mitochondrial NADH/NAD+ ratio and a reduced rate of 14CO2 production from [14C] fatty acids suggested restriction of the citric acid cycle. The higher glycogen and lipid levels were possibly the cause for the reduced cellular and vascular spaces found in cafeteria group livers, likely contributing to oxygen consumption restriction. In conclusion, specific substrates and gluconeogenic modulators contribute to a higher stimulation of gluconeogenesis in livers from the cafeteria group.

Tracking the carbons supplying gluconeogenesis

“…Studying fatty livers from rats given a high caloric diet and non-fatty livers from rats given a control diet, Junior et al studied glucose production rates by perfusing labeled gluconeogenic precursors [91]. Glycerol infusion led to increased glucose production rates in fatty livers while lactate and lactate plus pyruvate infusions decreased glucose production in fatty livers.…”

Glycerol induces G6pc in primary mouse hepatocytes and is the preferred substrate for gluconeogenesis both in vitro and in vivo

“…For example, glycerol is elevated in T2DM and predicts the worsening of hyperglycemia and insulin resistance (11–13). Livers of diet-induced obese rats also show higher rate of GNG from glycerol than from pyruvate and lactate (14), suggesting that glycerol may be a preferred substrate to pyruvate and lactate under some conditions.…”

Hepatoprotective effects ofErythrina abyssinicaLam Ex Dc against Non Alcoholic Fatty Liver Disease in Sprague Dawley Rats

“…We used a modified high fat/high sugar diet which was prepared by the addition of 0.8% monosodium-glutamate to a standard high-fat/high sugar diet. High-fat/high-sugar diets ("cafeteria diets") are a popular animal model for the induction of NAFLD and are normally administered chronically over a period of six to sixteen weeks [29]. However, high-fat/high-sugar diets administered ad-libitum normally have the limitation of reduced food consumption compared to normal rat chow and this has been attributed to reduced palatability and satiety induction in the cafeteria diets [30].…”