The Effect of a Sustained High-Fat Diet on the Metabolism of White and Brown Adipose Tissue and Its Impact on Insulin Resistance: A Selected Time Point Cross-Sectional Study.

(1) Background: studies on the long-term dynamic changes in fat depot metabolism in response to a high-fat diet (HFD) on hepatic lipid deposition and insulin resistance are sparse. This study investigated the dynamic changes produced by HFD and the production of dysfunctional fat depots on insulin resistance and liver lipid metabolism. (2) Methods: mice fed a chow or HFD (45% kcal fat) diet had three fat depots, liver, and blood collected at 6, 10, 20, and 30 weeks. Anthropometric changes and gene markers for adipogenesis, thermogenesis, ECM remodeling, inflammation, and tissue insulin resistance were measured. (3) Results: early responses to the HFD were increased body weight, minor deposition of lipid in liver, increased adipocyte size, and adipogenesis. Later changes were dysfunctional adipose depots, increased liver fat, insulin resistance (shown by changes in ITT) accompanied by increased inflammatory markers, increased fibrosis (fibrosis > 2-fold, p < 0.05 from week 6), and the presence of crown cells in white fat depots. Later, changes did not increase thermogenic markers in response to the increased calories and decreased UCP1 and PRDM16 proteins in WAT. (4) Conclusions: HFD feeding initially increased adipocyte diameter and number, but later changes caused adipose depots to become dysfunctional, restricting adipose tissue expansion, changing the brown/beige ratios in adipose depots, and causing ectopic lipid deposition and insulin resistance.

Constant-moderate versus high-intensity interval training on heart adiponectin levels in high-fat fed mice: a preventive and treatment approach.

CONTEXT: Research has described that adiponectin plays a key role in cardiomyocytes metabolism, however, the effects of exercise during obesity on cardiac adiponectin levels is unclear. OBJECTIVE: To investigate the effects of constant-moderate endurance (END) and high-intensity interval training (HIIT), on heart adiponectin levels in mice. MATERIAL AND METHODS: Two experiments were conducted: (1) preventive (EX1): 10 week-old male mice were fed standard (CHOW) or high-fat diet (HFD;45% fat) and simultaneously trained with END and HIIT for 10 weeks; (2) Treatment (EX2): after 10 weeks of dietary intervention, another cohort of 10 week-old mice were trained by both programmes for 10 weeks. RESULTS: In EX1, END and HIIT decreased low-molecular weight adiponectin (∼0.5-fold; p < 0.05) and increased GLUT4 levels (∼2-fold; p < .05). In EX2, HFD significantly decreased high-molecular weight adiponectin (∼0.7-fold; p < .05), and END reversed this change.Discussion and conclusion: HFD and exercise influence heart adiponectin isoforms and therefore might impact cardiomyocyte metabolism.

Does Inclusion of Mental Agility Test in Admission Exam Help Better Student Selection in the Health Professions Education Programs?

Academic ability test has been used predominantly in student selection of medical and allied health profession education programs in Nepal. But the use of academic performance as the single selection criterion puts the students from low socioeconomic background at greater disadvantage despite equal suitability due to the lack of adequate guidance and support during their schooling. To address this limitation, use of aptitude test i.e. both the general cognitive and non-cognitive ability tests that measures fluid intelligence and personality traits respectively has been practiced. The measurement of non-cognitive traits has been found to predict the clinical examination score. In Nepal, for the first time, Patan Academy of Health Sciences implemented the assessment of aptitude test (both cognitive and non-cognitive ability test) for the student selection in the undergraduate medical program. Since the inception, Medical Education Commission in Nepal embraced Mental Agility Test, a component of an aptitude test, along with the academic ability test for the nationwide common entrance test in all the undergraduate Health Professions Education Programs. This indeed is an innovative approach in student selection, but in the context of Nepal whether the use of these tools is appropriate in the entrance exam requires psychometric evaluation and further validation through graduates' performance after their enrolment. Keywords: Health professions education; mental agility test; student selection.

The Effect of TGFß1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation.

Transforming growth factor beta (TGFß) is a versatile cytokine. Although a profibrotic role of TGFß is well established, its effect on tissue inhibitor of metalloproteinase (TIMPs) and inflammatory mediators are incompletely described. This study investigates the profibrotic and pro-inflammatory role of TGFß1 during adipocyte differentiation. NIH3T3L1 cells were used for the in vitro study and were differentiated by adding a standard differentiation mix either with rosiglitazone (R-Diff) or without (S-Diff). Recombinant TGFß1 (2 ng/mL) was added to the undifferentiated preadipocyte during the commitment stage and at the terminal differentiation stage. TGFß1 treatment significantly decreased adiponectin mRNA at both early commitment (>300 fold) and terminal differentiated cells [S-Diff (~33%) or R-Diff (~20%)]. TGFß1 upregulated collagen VI mRNA and its regulators connective tissue growth factor (CCN2/CTGF), TIMP1 and TIMP3 mRNA levels in undifferentiated preadipocytes and adipocytes at commitment stage. But in the terminal differentiated adipocytes, changes in mRNA and protein of collagen VI and TIMP3 mRNA were not observed despite an increase in CCN2/CTGF, TIMP1 mRNA. Although TGFß1 upregulated interleukin-6 (IL6) and monocyte chemoattractant protein-1 (MCP1) mRNA at all stages of differentiation, decreased tumor necrosis factor-α (TNFα) mRNA was observed early in adipocyte differentiation. This study highlights the complex role of TGFß1 on extracellular matrix (ECM) remodeling and inflammatory markers in stimulating both synthetic and inhibitory markers of fibrosis at different stages of adipocyte differentiation.

Perception of Students and Faculty on Problem Based Learning in Proficiency Certificate Level Nursing Program.

BACKGROUND: Patan Academy of Health Sciences intended to implement problem based learning in proficiency certificate level nursing program who have just completed grade 10. Presently in Nepal, the available literature on use of problem based learning as teaching learning methods is limited to undergraduate medicine who have passed 10+2 or equivalent. It was conducted to measure the perception of students and faculty on problem based learning in nursing program. METHODS: Nursing faculty who have been involved in teaching learning of nursing curriculum were trained to conduct problem based learning and write problem based learning case. Prior to run problem based learning case, students were also oriented for the problem based learning process. A 44 students and seven faculty returned the filled data collection tool. RESULTS: Both the students and tutors perceived that the problem based learning is an effective teaching learning method. They also found that the attributes of problem based learning such as self-directed learning, collaborative learning, team work and fun learning. Students were eager to have more problem based learning session in their curriculum. Faculty also perceived that problem based learning can be a better teaching learning methods and it can be implemented in proficiency certificate level nursing. CONCLUSIONS: This study shows the acceptance of problem based learning as a teaching learning methods in proficiency certificate level nursing program by both the students and faculty.

Constant-Moderate and High-Intensity Interval Training Have Differential Benefits on Insulin Sensitive Tissues in High-Fat Fed Mice.

In a mouse model of diet-induced obesity, this study determined if two exercise prescriptions with equivalent time and distance covered, [constant-moderate endurance (END) and high intensity interval training (HIIT)], exert differential metabolic benefits on insulin sensitive tissues. Male 10 week old C57BL/6 mice were fed a high fat diet (HFD; 45% kcal fat) ad libitum for 10 weeks and for a further 10 weeks they underwent END or HIIT training (3 × 40 min sessions/wk). Untrained HFD and chow-fed mice acted as controls. At 30 weeks of age, mice were sacrificed and quadriceps muscle, subcutaneous adipose tissue (SAT) and liver were excised. Neither END nor HIIT altered body weight or composition in HFD mice. In quadriceps, HFD decreased high-molecular weight adiponectin protein, which was normalized by END and HIIT. In contrast, HIIT but not END reversed the HFD-driven decrease in the adiponectin receptor 1 (AdipoR1). In SAT, both programs tended to decrease collagen VI protein (p = 0.07-0.08) in HFD, whereas only HIIT induced an increase in the mRNA (3-fold vs. HFD untrained) and protein (2-fold vs. HFD untrained) of UCP1. In liver, only END reversed collagen I accumulation seen in HFD untrained mice. Our results suggest that HIIT may promote better systemic metabolic changes, compared to END, which may be the result of the normalization of muscle AdipoR1 and increased UCP1 seen in SAT. However, END was more effective in normalizing liver changes, suggesting differential metabolic effects of END and HIIT in different tissues during obesity.

Differential metabolic effects of constant moderate versus high intensity interval training in high-fat fed mice: possible role of muscle adiponectin.

Exercise regimens may have differing effects in the presence of obesity. In addition to being fat derived, adiponectin has recently been described as a myokine that regulates insulin sensitivity, which may link to exercise-related metabolic benefits in obesity. Whether skeletal muscle adiponectin varies in different exercise modalities is unclear. This study investigated the comparative effects of 10 weeks of endurance constant-moderate intensity exercise (END) with high intensity interval training (HIIT), on metabolic outcomes, including muscle adiponectin in a mouse model of diet-induced obesity. Ten-week-old male C57BL/6 mice were fed a high-fat diet (HFD) (45% FAT) or standard CHOW diet ab libitum and underwent one of three training regimes: (1) no exercise, (2) END, or (3) HIIT (8 bouts of 2.5 min with eight periods of rest of 2.5 min) for 10 weeks (3 × 40 min sessions/week). Chow-fed mice acted as controls. Compared with HFD alone, both training programs similarly protected against body weight gain (HFD = 45 ± 2; END = 37 ± 2; HIIT = 36 ± 2 g), preserved lean/fat tissue mass ratio (HFD = 0.64 ± 0.09; END = 0.34 ± 0.13; HIIT = 0.33 ± 0.13), and improved blood glucose excursion during an insulin tolerance test (HFD = 411 ± 54; END = 350 ± 57; HIIT = 320 ± 66 arbitrary units [AU]). Alterations in fasting glycemia, insulinemia, and AST/ALT ratios were prevented only by END. END, but not HIIT increased skeletal muscle adiponectin mRNA (14-fold; P < 0.05) and increased protein content of high molecular weight (HMW) adiponectin (3.3-fold), whereas HIIT induced a milder increase (2.4-fold). Compared with HFD, neither END nor HIIT altered circulating low (LMW) or high (HMW) molecular weight adiponectin forms. Furthermore, only END prevented the HFD downregulation of PGC1α (P < 0.05) mRNA levels downstream of muscle adiponectin. These data show that different training programs affect muscle adiponectin to differing degrees. Together these results suggest that END is a more effective regimen to prevent HFD-induced metabolic disturbances in mice.