Fibroblast growth factor-21 restores insulin sensitivity but induces aberrant bone microstructure in obese insulin-resistant rats.

Fibroblast growth factor (FGF)-21 is a potent endocrine factor that improves insulin resistance and obesity-associated metabolic disorders. However, concomitant activation of peroxisome proliferator-activated receptor-γ by FGF-21 makes bone susceptible to osteopenia and fragility fracture. Since an increase in body weight often induced adaptive change in bone by making it resistant to fracture, it was unclear whether FGF-21 would still induce bone defects in overweight rats. Therefore, the present study aimed to investigate bone microstructure and its mechanical properties in high fat diet (HF)-fed rats treated with 0.1 mg/kg/day FGF-21. Eighteen male rats were divided into two groups to receive either a normal diet or HF for 12 weeks. HF rats were then divided into two subgroups to receive either vehicle or FGF-21 for 4 weeks. The results showed that HF led to obesity, dyslipidemia and insulin resistance, as indicated by hyperinsulinemia with euglycemia. In HF rats, there was an increase in tibial yield displacement (an indicator of ability to be deformed without losing toughness, as determined by 3-point bending) without changes in tibial trabecular volumetric bone mineral density (vBMD) or cortical bone parameters, e.g., cortical thickness and bone area. FGF-21 treatment strongly improved the metabolic parameters and increased insulin sensitivity in HF rats. However, FGF-21-treated HF rats showed lower yield displacement, trabecular vBMD, trabecular bone volume, trabecular thickness, and osteoblast surface compared with vehicle-treated HF rats. These findings suggest that, despite being a potent antagonist of insulin resistance and visceral fat accumulation, FGF-21 is associated with bone defects in HF rats.

The roles of metabolic thermogenesis in body fat regulation in striped hamsters fed high-fat diet at different temperatures.

The metabolic thermogenesis plays important roles in thermoregulation, and it may be also involved in body fat regulation. The thermogenesis of brown adipose tissue (BAT) is largely affected by ambient temperature, but it is unclear if the roles in body fat regulation are dependent on the temperature. In the present study, uncoupling protein 1 (ucp1)-based BAT thermogenesis, energy budget and body fat content were examined in the striped hamsters fed high fat diet (HF) at cold (5°C) and warm (30°C) temperatures. The effect of 2, 4-dinitrophenol (DNP), a chemical uncoupler, on body fat was also examined. The striped hamsters showed a notable increase in body fat following the HF feeding at 21°C. The increased body fat was markedly elevated at 30°C, but was significantly attenuated at 5°C compared to that at 21°C. The hamsters significantly increased energy intake at 5°C, but consumed less food at 30°C relative to those at 21°C. Metabolic thermogenesis, indicated by basal metabolic rate, UCP1 expression and/or serum triiodothyronine levels, significantly increased at 5°C, but decreased at 30°C compared to that at 21°C. A significant decrease in body fat content was observed in DNP-treated hamsters relative to the controls. These findings suggest that the roles of metabolic thermogenesis in body fat regulation largely depend on ambient temperature. The cold-induced enhancement of BAT thermogenesis may contribute the decreased body fat, resulting in a lean mass. Instead, the attenuation of BAT thermogenesis at the warm may result in notable obesity.

The Impact of DJOS Surgery, a High Fat Diet and a Control Diet on the Enzymes of Glucose Metabolism in the Liver and Muscles of Sprague-Dawley Rats.

The prevalence of diabetes type 2 (T2DM) and obesity is growing exponentially and becoming a global public health problem. The enzymes of glucose metabolism play a role in the pathogenesis of insulin resistance and T2DM. A pathophysiological link between different dietary patterns, HFD, obesity, T2DM and the enzymes of glucose metabolism can be used as a potential target in therapeutic strategies for the treatment of obesity, and T2DM. The aim of this study was to measure the impact of DJOS bariatric surgery and different types of dietary patterns on glycogen synthase kinase 3 α (GSK-3α), glycogen phosphorylase (PYGM, PYGL), and phosphofructokinase (PFK-1) concentrations in liver and soleus muscle tissues of rats. After 8 weeks on a high-fat diet (HF) or control diet (CD), rats underwent duodenal-jejunal omega switch (DJOS) or SHAM (control) surgery. After surgery, for the next 8 weeks, half of DJOS/SHAM animals were kept on the same diet as before, and half had a changed diet. The concentrations of GSK-3α, PYGM, PYGL and PFK-1 were measured in the soleus muscles and livers of the Sprague-Dawley rats. The type of diet applied before/after surgery had stronger impact on levels of selected metabolic enzymes than DJOS or SHAM surgery. The impact of DJOS surgery was visible for GSK-3α and PYGL concentration in the liver but not in the soleus muscle tissue. The type of bariatric surgery had an impact on liver GSK-3α concentration in all studied groups except the CD/CD group, where the impact of diet was stronger. DJOS bariatric surgery influenced the level of PYGL in the livers of rats maintained on the CD/CD diet but not from other groups. The dietary patterns applied before and after bariatric surgery, had a stronger impact on enzymes' concentrations than DJOS surgery, and the strong, deleterious effect of an HF was observed. A change of the diet per se showed a negative impact on the enzymes' tissue concentration.

Vitis thunbergii var. taiwaniana Extracts and Purified Compounds Ameliorate Obesity in High-Fat Diet-Induced Obese Mice.

The increasing prevalence of obesity continues to gain more attention worldwide. In this study, diet-induced obese mice were used to evaluate the antiobesity effects of extracts, fractions, and purified compounds from Vitis thunbergii var. taiwaniana (VTT). The C57BL/6J mice were fed a 5-week high-fat diet (HF) concurrently with ethanol extracts (Et-ext, 80 mg/kg) from roots (R), stems (S), and leaves (L) by oral gavage daily. Only R-Et-ext interventions showed significant weight reduction in mice compared with those in the HF group; however, mouse plasma contents of total cholesterols (TC), total triglycerides (TG) and low-density lipoproteins (LDL) of all three Et-ext intervened groups showed significant reductions compared with those in the HF group. Furthermore, intervention with the ethyl acetate-partitioned fraction (EA-fra, 60 mg/kg) from R-Et-ext but not the n-butanol-partitioned fraction or water fraction from R-Et-ext showed significant weight reduction in mice compared with those in the HF group. The same molecular weights of three resveratrol tetramers, (+)-hopeaphenol, (+)-vitisin A, and (-)-vitisin B, were isolated from the EA-fra of VTT-R. The (+)-vitisin A and fenofibrate (25 mg/kg) but not the (+)-hopeaphenol and (-)-vitisin B interventions showed significant weight reduction in mice compared with those in the HF group. The total feed intake among the HF groups with or without interventions showed no significant differences. The mouse plasma contents of TC, TG, LDL, free fatty acid, and plasma lipase activity of the three resveratrol tetramer-intervened groups showed reductions in the mice compared with those in the HF group. It was proposed that the lipase inhibitory activities of VTT extracts and purified resveratrol tetramers might contribute in part to the antiobesity effect, and these results suggested that VTT may be developed as functional food for achieving antiobesity objectives and requires further investigation.