Eating behavior.

<p>Parameters during day- and night-time at 14 weeks after gastric bypass (GB), 8 weeks after duodenal switch (DS) and 8–14 weeks after laparotomy (LAP). Data are expressed as mean ± SEM. *: <i>p</i><0.05, **: <i>p</i><0.01, ***: <i>p</i><0.001 between LAP <i>vs.</i> GB or DS. ^†: <i>p</i><0.05, ^††: <i>p</i><0.01, ^†††: <i>p</i><0.001 between GB <i>vs.</i> DS.</p

Body weight.

<p>Naïve rats (data from Taconic), rats that underwent laparotomy (LAP) at 13 weeks (LAP) and rats that have had high-fat since 5 weeks of age (data from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072896#pone.0072896-Furnes3" target="_blank">[31]</a>) (<b>A</b>)<b>.</b> Rats after gastric bypass (GB), duodenal switch (DS) and laparotomy (LAP) (<b>B</b>). Data are expressed as means ± SEM. **: <i>p</i><0.01, ***: <i>p</i><0.001 between LAP <i>vs.</i> GB or DS.</p

Food intake.

<p>Total food intake (kcal/rat) (<b>A,B</b>) and relative food intake (kcal/100 g body weight) (<b>C,D</b>) during day- and night-time. Short-term after surgery: 3 weeks after gastric bypass (GB), 2 weeks after duodenal switch (DS) or 2–3 weeks after lapatoromy (LAP). Long-term after surgery: 14 weeks after GB, 8 weeks after DS or 8–14 weeks after LAP. Data are expressed as means ± SEM. *: <i>p</i><0.05, **: <i>p</i><0.01, ns: not significant between LAP (n = 13) <i>vs.</i> GB (n = 8) or DS (n = 5).</p

Fecal energy density.

<p>Three weeks after gastric bypass (GB) or laparotomy (LAP_GB) (<b>A</b>) and eight weeks after duodenal switch (DS) or laparotomy (LAP_DS) (<b>B</b>). Data are expressed as mean ± SEM. **: <i>p</i><0.01, ns: not significant between LAP_GB (n = 7) <i>vs.</i> GB (n = 8) or LAP_DS (n = 6) <i>vs.</i> DS (n = 5).</p

Schematic drawing of anatomy.

<p>The gastrointestinal tract of human (<b>A–D</b>) and rat (<b>E–H</b>) before (<b>A, E</b>) and after Roux-en-Y gastric bypass (GB) (<b>B, F</b>), mini-GB (<b>C, G</b>), and duodenal switch (<b>D, H</b>)<b>.</b> Glandular stomach is indicated by grid gray and jejunum by light grid gray. The rumen of rat stomach is non-glandular (white area). Note: In <b>A, E</b>, percentages mean % of small intestine, e.g. in <b>E</b>, jejunum is 90% of total small intestine in rats based on <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072896#pone.0072896-DeSesso1" target="_blank">[11]</a>; in <b>F</b>, rat Roux-en-Y GB <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072896#pone.0072896-Stylopoulos1" target="_blank">[3]</a>, and in <b>G</b>, Mini-GB used in the present study.</p

Eating behavior.

<p>Satiety ratio (min/g) (<b>A,B</b>) and rate of eating (g/min) (<b>C,D</b>) during day- and night-time<b>.</b> Short-term after surgery: 3 weeks after gastric bypass (GB), 2 weeks after duodenal switch (DS) or 2–3 weeks after lapatoromy (LAP). Long-term after surgery: 14 weeks after GB, 8 weeks after DS or 8–14 weeks after LAP. Data are expressed as means ± SEM. ***: <i>p</i><0.001, ns: not significant between LAP (n = 13) <i>vs.</i> GB (n = 8) or DS (n = 5).</p

Energy expenditure during day- and night-time.

<p>Short-term after surgery: 3 weeks after gastric bypass (GB), 2 weeks after duodenal switch (DS) or 2–3 weeks after laparotomy (LAP). Long-term after surgery: 14 weeks after GB, 8 weeks after DS or 8–14 weeks after LAP. Data are expressed as means ± SEM. *: <i>p</i><0.05, **: <i>p</i><0.01, ***: <i>p</i><0.001, ns: not significant between LAP_GB (n = 7) <i>vs.</i> GB (n = 8) or LAP_DS (n = 6) <i>vs.</i> DS (n = 5).</p

Metabolism.

<p>Parameters during day- and nighttime at 14 weeks after gastric bypass (GB) and the age-matched laparotomy-operated group (LAP_GB), and at 8 weeks after duodenal switch (DS) and the age-matched laparotomy-operated group (LAP_DS). Data are expressed as means ± SEM. *: <i>p</i><0.05, **: <i>p</i><0.01, ***: <i>p</i><0.001 between LAP_GB<i>vs.</i> GB or LAP_DS<i>vs.</i> DS.</p

Profiles of the functions , , and .

<p>Thresholds of necroxia, hypoxia and normoxia are marked as , and , respectively.</p

Schematic diagram of the roles of ROS, GSH, and hydrogen ions in cancer cell growth and tumor angiogenesis.

<p>(i) ROS is a major by-product of aerobic metabolism and plays a dual role in cancer cell life-cycle: below a certain threshold, increasing amounts of ROS promotes cell proliferation through pathways of extracellular-signal-regulated kinases (ERKs) and cell survival factors such as Akt. However, ROS leads to cell apoptosis when its concentration is over the toxic threshold. Additionally, ROS may play a function in up-regulating HIF-1 expression, which in turn results in increasing the production of angiogenesis factor VEGF. (ii) GSH (glutathione) is the most abundant antioxidant produced by cancer cells to protect themselves from oxidative stress; it can remove ROS (mostly ) with the help of enzyme . (iii) Large amount of hydrogen ions are produced as a consequence of glucose metabolism, and are pumped out by abnormally expressed proton transporters. There is evidence indicating that acidic extracellular environment induces VEGF production through the ERK/MAPK signaling pathway.</p