Fermentable carbohydrate alters hypothalamic neuronal activity and protects against the obesogenic environment.

Obesity has become a major global health problem. Recently, attention has focused on the benefits of fermentable carbohydrates on modulating metabolism. Here, we take a system approach to investigate the physiological effects of supplementation with oligofructose-enriched inulin (In). We hypothesize that supplementation with this fermentable carbohydrate will not only lead to changes in body weight and composition, but also to modulation in neuronal activation in the hypothalamus. Male C57BL/6 mice were maintained on a normal chow diet (control) or a high fat (HF) diet supplemented with either oligofructose-enriched In or corn starch (Cs) for 9 weeks. Compared to HF+Cs diet, In supplementation led to significant reduction in average daily weight gain (mean ± s.e.m.: 0.19 ± 0.01 g vs. 0.26 ± 0.02 g, P < 0.01), total body adiposity (24.9 ± 1.2% vs. 30.7 ± 1.4%, P < 0.01), and lowered liver fat content (11.7 ± 1.7% vs. 23.8 ± 3.4%, P < 0.01). Significant changes were also observed in fecal bacterial distribution, with increases in both Bifidobacteria and Lactobacillius and a significant increase in short chain fatty acids (SCFA). Using manganese-enhanced MRI (MEMRI), we observed a significant increase in neuronal activation within the arcuate nucleus (ARC) of animals that received In supplementation compared to those fed HF+Cs diet. In conclusion, we have demonstrated for the first time, in the same animal, a wide range of beneficial metabolic effects following supplementation of a HF diet with oligofructose-enriched In, as well as significant changes in hypothalamic neuronal activity.

Metabolic profiling of the rat liver after chronic ingestion of alpha-naphthylisothiocyanate using in vivo and ex vivo magnetic resonance spectroscopy.

Certain human diseases affecting the biliary tree can be modeled in rats by ingestion of the hepatobiliary toxin alpha-naphthylisothiocyanate (ANIT). Phosphorus magnetic resonance spectroscopy (MRS) allows the noninvasive monitoring of cell dynamics through detection of phosphodiesters (PDE) and phosphomonoesters (PME). Hepatic (31)P MRS techniques were therefore used to study the toxic effects of low-dose chronic ANIT ingestion, with a view toward providing biomarkers sensitive to hepatobiliary dysfunction and cholestatic liver injury. Rats were fed an ANIT supplemented diet at three doses (ANIT_0.05%, ANIT_0.04%, and ANIT_0.025%) for 2 weeks. Data from in vivo MRS were compared with results from pair-fed controls (PFCs). Blood and tissue samples were collected at 2 weeks for clinical chemistry, histology, and (1)H magic angle spinning MRS. Increases in PDE, relative to total phosphorus (tPh), were detected in both the ANIT_0.05% and ANIT_0.04% groups (0.07 ± 0.01 and 0.08 ± 0.01, respectively) relative to PFC groups (0.03 ± 0.01 and 0.05 ± 0.01, respectively). An increase in PME/tPh was observed in the ANIT_0.05% group only (0.17 ± 0.02) relative to PFC_0.05% (0.12 ± 0.01). Ex vivo (1)H MRS findings supported this, wherein measured phosphocholines (PCs) were increased in ANIT_0.05% and ANIT_0.04% groups. Increases in relative total choline (tCho) distinguished the ANIT_0.05% group from the ANIT_0.04% group. Markers of hepatotoxicity such as raised total bilirubin and alkaline phosphatase were found at all ANIT doses. Histological findings included a dose-related increase in both severity of biliary hyperplasia and focal hepatocellular necrosis. Here, we found that ANIT-induced moderate hepatobiliary dysfunction was associated with a relative increase in phosphodiesters in vivo and PCs ex vivo. Raised PME/tPh in vivo and tCho ex vivo were also present at high doses corresponding to a higher incidence of marked biliary hyperplasia and moderate hepatocellular necrosis.

Cerebral activation by fasting induces lactate accumulation in the hypothalamus.

Carbon-13 ((13)C) high-resolution magic angle spinning (HR-MAS) spectroscopy was used to investigate the neuroglial coupling mechanisms underlying appetite regulation in the brain of C57BL/6J mice metabolizing [1-(13)C]glucose. Control fed or overnight fasted mice received [1-(13)C]glucose (20 micromol/g intraperitoneally [i.p.]), 15 min prior to brain fixation by focused microwaves. The hypothalamic region was dissected from the rest of the brain and (13)C HR-MAS spectra were obtained from both biopsies. Fasting resulted in a significant increase in hypothalamic [3-(13)C]lactate and [2-(13)C]gamma-aminobutyric acid (GABA) relative to the remaining brain. Administration of the orexigenic peptide ghrelin (0.3 nmol/g i.p.) did not increase hypothalamic [3-(13)C]lactate or [2-(13)C]GABA, suggesting that ghrelin signaling is not sufficient to elicit all the metabolic consequences of hypothalamic activation by fasting. Our results indicate that the hypothalamic regulation of appetite involves, in addition to the well-known neuropeptide signaling, increased neuroglial lactate shuttling and augmented GABA concentrations.