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(C) Correlation of mean daily food intake and weight gain of 4-month-old mice fed HCD during a 10-day period (r Beyond increased calorie consumption, excess adiposity may also reflect differences in digestion, nutrient absorption, and/or energy mobilization/expenditure.In the context of the central role of dietary fat in obesity (), lipid digestion was identical between genotypes, and triglycerides were unmeasurable (completely digested), while free fatty acid levels were comparable in stool (Figure 4A).In contrast, lean body mass and total body water were equivalent between genotypes (Figure 1, E and F).Hypertrophy of adipose mass in Gucy2c mice was associated with hepatic steatosis (Figure 2, A and B) and elevated serum leptin (Figure 2C), an adipocyte-derived peptide whose circulating level reflects fat mass.

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This endocrine prohormone signal is selectively decoded centrally by specific proteolytic liberation of uroguanylin, but not guanylin, unexpectedly activating neuronal GUCY2C and downstream anorexigenic pathways.Furthermore, GUCY2C deficiency amplified the metabolic syndrome associated with diet-induced obesity, including cardiac hypertrophy (Figure 2D), hyperleptinemia (Figure 2, E and F), hyperinsulinemia (Figure 2G), and impaired glycemic control (Figure 2H).



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