Mouse models designed to examine hepatic metabolism are critical to diabetes and obesity research. Thus, a microscale method to quantitatively assess hepatic glucose and intermediary metabolism in conscious, unrestrained mice was developed. [(13)C3]propionate, [(2)H2]water, and [6,6-(2)H2]glucose isotopes were delivered intravenously in short- (9 h) and long-term-fasted (19 h) C57BL/6J mice. GC-MS and mass isotopomer distribution (MID) analysis were performed on three 40-μl arterial plasma glucose samples obtained during the euglycemic isotopic steady state. Model-based regression of hepatic glucose and citric acid cycle (CAC)-related fluxes was performed using a comprehensive isotopomer model to track carbon and hydrogen atom transitions through the network and thereby simulate the MIDs of measured fragment ions. Glucose-6-phosphate production from glycogen diminished, and endogenous glucose production was exclusively gluconeogenic with prolonged fasting. Gluconeogenic flux from phosphoenolpyruvate (PEP) remained stable, whereas that from glycerol modestly increased from short- to long-term fasting. CAC flux [i.e., citrate synthase (VCS)] was reduced with long-term fasting. Interestingly, anaplerosis and cataplerosis increased with fast duration; accordingly, pyruvate carboxylation and the conversion of oxaloacetate to PEP were severalfold higher than VCS in long-term fasted mice. This method utilizes state-of-the-art in vivo methodology and comprehensive isotopomer modeling to quantify hepatic glucose and intermediary fluxes during physiological stress in mice. The small plasma requirements permit serial sampling without stress and the affirmation of steady-state glucose kinetics. Furthermore, the approach can accommodate a broad range of modeling assumptions, isotope tracers, and measurement inputs without the need to introduce ad hoc mathematical approximations.

Background: AMPK is implicated as the mediator of AICAR action on liver metabolism. Results: AICAR suppresses glucose production independent of AMPK. Regulation of mitochondrial function is AMPK-dependent. Conclusion: Nucleotide monophosphates rely on AMPK to regulate energy metabolism but not to suppress glucose production. Significance: Targeted AMPK activation will not lower glucose production in metabolic diseases but could improve hepatic energetics.

Of all the edible oils, only that produced from olives has had its health attributes studied in detail. For maximum nutritional benefit, an edible oil should contain minimal levels of saturated fats, especially lauric and myristic acids and minimal levels of trans fatty acids. If the oils are not to be heated repeatedly and if they contain high levels of antioxidants, they should contain omega‐3 and possibly omega‐6 polyunsaturated fatty acids. The fatty acid profile should be dominated by monounsaturated fatty acids. Secondary products which act as antioxidants including polyphenols, proanthocyanidins, tocopherols and carotenoids increase the shelf‐life of oils, reportedly reduce cardiovascular disease and provide some anticarcinogenic properties. More research is also required, but there is evidence that phytosterols and squalene are also beneficial components of edible oils. Selection and breeding can be used to increase the desirable components of edible oils. Geographic, culture and environmental factors can influence the properties of the oil produced by crops, and methods of processing can greatly reduce the levels of health promoting components. Despite the current anti‐GMO sentiments, biotechnology should be used both in the development of plant cultivars which produce nutritional oils and in processing to maximize the desirable components.

AMPK is an energy sensor that protects cellular energy state by attenuating anabolic and promoting catabolic processes. AMPK signaling is purported to regulate hepatic gluconeogenesis and substrate oxidation; coordination of these processes is vital during nutrient deprivation or pathogenic during overnutrition. Here we directly test hepatic AMPK function in regulating metabolic fluxes that converge to produce glucose and energy in vivo. Flux analysis was applied in mice with a liver-specific deletion of AMPK (L-KO) or floxed control littermates to assess rates of hepatic glucose producing and citric acid cycle (CAC) fluxes. Fluxes were assessed in short and long term fasted mice; the latter condition is a nutrient stressor that increases liver AMP/ATP. The flux circuit connecting anaplerosis with gluconeogenesis from the CAC was unaffected by hepatic AMPK deletion in short and long term fasting. Nevertheless, depletion of hepatic ATP was exacerbated in L-KO mice, corresponding to a relative elevation in citrate synthase flux and accumulation of branched-chain amino acid-related metabolites. L-KO mice also had a physiological reduction in flux from glycogen to G6P. These results demonstrate AMPK is unnecessary for maintaining gluconeogenic flux from the CAC yet is critical for stabilizing liver energy state during nutrient deprivation.

The objective of this study was to determine the health benefits of extra-virgin and refined olive oils, which are high in mono-unsaturated fatty acids (MUFAs) and polyphenolic compounds using the pig as a model. Thirty-two cross-bred pigs were individually penned, allocated to one of four dietary treatments and fed ad libitum for 28 days. Two of the experimental diets consisted of a basal diet containing 12% tallow and either 7% sunflower oil (TSO) or 7% extra-virgin olive oil (TEVO) on a w/w basis. The remaining diets contained 19% extra-virgin olive oil (EVO) or 19% of refined olive oil (RO). On days 7, 14 and 28 fasted and 3-h post-prandial blood samples were taken. Body composition was measured at the beginning and end of the study using dual energy X-ray absorptiometry. Daily gain, feed intake and lean and fat deposition were not significantly different between the treatments. However, the daily increase in bone mineral density was higher in pigs fed diets containing olive oil (1.23 vs 2.54, 6.28, 5.20 mg cm −2 per day for TSO, TEVO, EVO and RO, respectively, P = 0.050). Both fasting and non-fasting plasma triglycerides were lower (P = 0.003) in pigs fed MUFA-rich diets, while the cholesterol profile was not significantly different between the treatments. The results from in vitro copper-induced lipid peroxidation, expressed in terms of conjugated dienes, showed that low density lipoprotein (LDL) particles in postprandial serum from pigs fed olive oil were moderately more resistant to oxidative modification. In conclusion, these data demonstrate that both extra-virgin and refined olive oils attenuate postprandial hypertriglyceridaemia, moderately affect oxidation susceptibility and increase bone mineral density in growing pigs.