MGAT2-deficient mice are protected from obesity induced by high-fat feeding. (a,b) Growth curves of male mice on a regular diet (10% calories from fat; a) or switched to a high-fat diet (60% calories from fat; underlined; b) at 9 weeks of age. n = 8–16 mice per group. *P < 0.01 versus wild type. (c) Body composition of 5–6-month-old male mice, as determined by DEXA. n = 12–16 mice per group. **P < 0.001 versus wild type fat mass. (d) Weight gain of 4–6-month-old female mice fed a regular diet and then switched to a high-fat diet (underlined) for 12 weeks. n = 8 mice per group. *P < 0.01 versus wild type. Values are means ± s.e.m.

MGAT2-deficient mice are protected from metabolic disorders induced by high-fat feeding. (a) Protection from hyperinsulinemia and glucose intolerance. Fasting plasma insulin (top) and blood glucose concentrations (bottom) of 8–11-month-old male wild-type and Mogat2^−/− mice fed chow (n = 6 and 10, respectively), a high-fat diet for 2 months (n = 9 per group), or a high-fat diet for 7–9 months (8-month HF, n = 13 and 12, respectively) after an intraperitoneal injection of glucose (1 mg per g body weight). (b) Protection from hypercholesterolemia. Plasma cholesterol concentrations of mice fasted for 4 h. Solid bars represent high-density lipoprotein (HDL) cholesterol (same number of mice per group as in a). (c) Protection from hepatic steatosis. Representative appearance (top) and osmium tetroxide–toluidine blue–stained sections (bottom) of livers from wild-type and Mogat2^−/− mice fed a high-fat diet for 7–8 months. Scale bar, 100 μm. Values are means ± s.e.m. *P < 0.01 versus wild type.

MGAT2-deficient mice show increased energy expenditure and body temperature. (a) Food intake in wild-type and Mogat2^−/− mice. Cumulative food intake (left) and weight gain (right) of adult male mice (6–7 months old) during a 1-week period after being acclimated to individual housing and a 60% high-fat diet for a week. wild-type, n = 15; Mogat2^−/−, n = 11. (b) Oxygen consumption in wild-type and Mogat2^−/− mice. Male mice (5–6 months old) were acclimated individually in metabolic cages, and experiments were performed for 3 d on 10% fat (chow) or 60% fat (high-fat) diet. Data were normalized by lean body mass and were averages of light or dark phases from 3-day measurements. n = 12 per group. (c) Levels of physical activity in wild-type and Mogat2^−/− mice. Activity was assessed by breaks of light beams, and experiments were performed as described in b. (d) Body temperature in wild-type Mogat2^−/− mice fed the indicated diet under fasted or fed condition. n = 12–25 mice per group. Values are means ± s.e.m. *P < 0.01 and **P < 0.001 versus wild type.

Fat absorption in MGAT2-deficient mice is quantitatively normal but delayed.
(a) Intestinal fat absorption measured in adult mice fed a diet containing 60% of calories from fat. A nonabsorbable fat was used as a marker. Wild-type, n = 12; Mogat2^−/−, n = 14.
(b) Output and energy content determined by an adiabatic bomb calorimeter of feces from mice fed a 60% fat diet. Wild-type n = 9; Mogat2^−/−, n = 8. (c) Total amounts of retinol and retinyl esters (Vit. A) in the liver and the levels of α-tocopherol (Vit. E) in the WAT in 10-month-old male wild-type and Mogat2^−/− mice fed a 60 kcal% fat diet. n = 6 mice per group.
(d) Lipids extracted from the intestinal mucosa of mice fed a high-fat diet for 2 d, resolved by thin-layer chromatography using a two-solvent system and stained with iodine vapor. TG, triacylglycerol; DG, diacylglycerol; MG, monoacylglycerol; FA, fatty acid. (e) Plasma triacylglycerol and radioactivity levels in chow-fed female mice after injection of the lipase inhibitor tyloxapol and gavage with olive oil containing ¹⁴C-trioleoylglycerol. Wild-type, n = 7; Mogat2^−/− n = 6. (f) Sections of jejunum from mice fed a high-fat diet. Arrows indicate lipid droplets stained with toluidine blue. Scale bar, 20 μm. (g) Altered distribution of dietary triacylglycerol in the small intestine of Mogat2^−/− mice after an oral challenge of oil. Radioactivity levels 2 h after gavage with oil containing ¹⁴C-trioleoylglycerol in intestinal segments of female mice acclimatized to a high-fat diet. n = 4 per genotype. (h) Postprandial GLP-1 and PYY concentrations in the plasma of chronically high-fat–fed mice. n = 10–20 mice per group. Values are means ± s.e.m. *P < 0.05 and **P < 0.001 versus wild type.