Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice

Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers of de novo lipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγ and SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO2) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation in de novo lipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse

Soy protein improves tibial whole-bone and tissue-level biomechanical properties in ovariectomized and ovary-intact, low-fit female rats

Background: Osteoporosis and related fractures, decreased physical activity, and metabolic dysfunction are serious health concerns for postmenopausal women. Soy protein might counter the negative effects of menopause on bone and metabolic health due to the additive or synergistic effects of its bioactive components. Objective: To evaluate the effects of ovariectomy (OVX) and a soy-protein diet (SOY) on bone outcomes in female, low-capacity running (LCR) rats selectively bred for low aerobic fitness as a model of menopause. Methods: At 27 weeks of age, LCR rats (N = 40) underwent OVX or sham (SHAM) surgery and were randomized to one of two isocaloric and isonitrogenous plant-protein-based dietary treatments: 1) soy-protein (SOY; soybean meal); or, 2) control (CON, corn-gluten meal), resulting in four treatment groups. During the 30-week dietary intervention, animals were provided ad libitum access to food and water; body weight and food intake were measured weekly. At completion of the 30-week intervention, body composition was measured using EchoMRI; animals were fasted overnight, euthanized, and blood and hindlimbs collected. Plasma markers of bone formation (osteocalcin, OC; N-terminal propeptide of type I procollagen, P1NP) and resorption (tartrate-resistant acid phosphatase, TRAP5b; C-terminal telopeptide of type I collagen, CTx) were measured using ELISA. Tibial trabecular microarchitecture and cortical geometry were evaluated using μCT; and torsional loading to failure was used to assess cortical biomechanical properties. Advanced glycation end-product (AGE) content of the femur was measured using a fluorimetric assay, and was expressed relative to collagen content measured by a colorimetric OH-proline assay. Two-factor ANOVA or ANOVCA was used to test for significant main and interactive effects of ovarian status (OV STAT: OVX vs. SHAM) and DIET (SOY vs. CON); final body weight was included as a covariate for body-weight-dependent cortical geometry and biomechanical properties. Results: OVX had significantly greater CTx than SHAM; SOY did not affect bone turnover markers. OVX adversely affected trabecular microarchitecture as evidenced by reduced BV/TV, trabecular thickness (Tb.Th), trabecular number (Tb.N), and connectivity density (Conn.D), and by increased trabecular separation (Tb.Sp) and structural model index (SMI). SOY increased BV/TV only in ovary-intact animals. There was no effect of OVX or SOY on tibial cortical geometry. In SHAM and OVX rats, SOY significantly improved whole-bone strength and stiffness; SOY also increased tissue-level stiffness and tended to increase tissue-level strength (p = 0.067). There was no effect of OVX or SOY on AGE content. Conclusion: Soy protein improved cortical bone biomechanical properties in female low-fit rats, regardless of ovarian hormone status. Keywords: Osteoporosis, Menopause, Soy protein, Ovariectomy, Bon