Poor dietary habits contribute to increased incidences of obesity and related co-morbidities, such as type 2 diabetes (T2D). The biological, genetic, and pathological implications of T2D, are commonly investigated using animal models induced by a dietary intervention. In spite of significant research contributions, animal models have limitations regarding the translation to human pathology, which leads to questioning their clinical relevance. Important considerations include diet-specific effects on whole organism energy balance and glucose and insulin homeostasis, as well as tissue-specific changes in insulin and glucose tolerance. This review will examine the T2D-like phenotype in rodents resulting from common diet-induced models and their relevance to the human disease state. Emphasis will be placed on the disparity in percentages and type of dietary fat, the duration of intervention, and whole organism and tissue-specific changes in rodents. An evaluation of these models will help to identify a diet-induced rodent model with the greatest clinical relevance to the human T2D pathology. We propose that a 45% high-fat diet composed of approximately one-third saturated fats and two-thirds unsaturated fats may provide a diet composition that aligns closely to average Western diet macronutrient composition, and induces metabolic alterations mirrored by clinical populations.

Wheel running behavior was reduced significantly after orchidectomy and remained low after initial treatment with estrogens, but recovered to near control levels after 2 wk of exposure to estrogens. The estrogenic mechanism regulating wheel running behavior in male mice appears to induce an extensive but slow acting biological mechanism. Understanding the biological drive behind this mechanism may aid in developing useful therapeutic strategies to combat health issues related to physical inactivity.

BackgroundMicro‐RNAs (miRNAs) are a class of small, non‐protein coding RNAs that posttranscriptionally regulate gene expression through the degradation or translational inhibition of their target complimentary messenger RNAs (mRNAs). Developing evidence indicates the importance of miRNAs in the myogenic program and their influence on disorders affecting muscle growth and metabolism.PurposeThe purpose of this study was to determine whether miR23a regulates myotube formation in skeletal muscle under lipid‐induced atrophic conditions.MethodsC2C12 myoblasts were transfected with a mimic complex to increase levels of miR23a or vehicle at seeding, then induced to differentiate into myotubes. Cells were treated with palmitic acid (0.1mM) at day 0 and day 2 of differentiation. Cells were collected at day 4 of differentiation. Real‐time PCR was used to investigate changes in miRNA expression and myosin heavy chain staining was performed to determine differences in myotube formation.ResultsCells that received mimic had increases in miR‐23a levels. Palmitic acid‐induced reductions in myotube formation were abrogated with overexpression of miR‐23a.ConclusionsThese data suggest that miR23a may exist in a regulatory pathway that alters muscle growth in the presences of saturated fatty acid. Future work is ongoing to understand the mechanisms by which miR23a may regulate skeletal muscle growth under lipid‐induced atrophic conditions.Support or Funding InformationFaculty Research GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Physical inactivity is associated with elevated risks for many chronic diseases and premature death. Both rodent and human studies indicate that sex steroids—testosterone and estrogen—play a role in the biological regulation of physical activity. The sex steroids likely affect brain physiology and/or the cellular condition of the skeletal muscle of the hind limb muscles used to complete a wheel running task. Differences in speed patterns between physiologically different sex steroid levels may indicate a deficiency in the skeletal muscle's capability to effectively contract during wheel running, while differences in the accumulated duration pattern during wheel running may indicate a deficiency in central motivation to complete a prolonged wheel running bout. The purpose of this study was to assess wheel running speed and duration patterns in male C57BL/6J mice under normal and physiologically‐deficient testosterone conditions. Wheel running data were collected for ten days (n=14 physiologically normal; n=12 testosterone deficient) and each wheel revolution was counted and time‐stamped to accumulate a daily turn‐by‐turn wheel revolution record. Testosterone deficiency was induced via bilateral orchidectomy ten‐days prior to wheel running assessment. Ten‐day average speed (m·min−1) and accumulated duration (% of total activity during the dark period) were assessed in four 3‐hour epochs during the dark period (epoch 1: 6pm–9pm, epoch 2: 9pm–12am, epoch 3: 12am–3am, epoch 4: 3am–6am). Differences in speed and duration data across epochs and between treatment groups were compared by separate 4 × 2 mixed‐design ANOVAs. Wheel running speed was significantly [F(3,72)=6.5, p=0.001] different across epochs and between treatments. Wheel running speed remained consistent across all epochs in intact mice but decreased from a zenith during the initial epoch (mean±sd: 30.1±5.0 m·min−1) to a nadir (26.9±3.8 m·min−1) in deficient animals during the latter epochs. Intact mice ran faster (31.4±2.8 m·min−1) than deficient mice (26.1±5.4 m·min−1) throughout the dark period as a whole. Wheel running duration was significantly [F(3,72)=28.8, p<0.001] different across epochs and between treatments. The intact mice recorded higher percentages of wheel running during the initial epoch and decreased as the dark period progressed. Testosterone deficient mice ran the most (highest percentages) during the first and last epochs. In conclusion, wheel running patterns were significantly different following alteration to circulating testosterone levels in male mice. Changes in speed and duration patterns during wheel running indicate that both brain physiology and the cellular composition of skeletal muscle may be affected by the loss of testosterone.Support or Funding InformationThis project was supported by the Pilgram Marpeck School of STEM intramural research fund at Truett McConnell University.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

BackgroundMicroRNAs (miRs) are non‐protein coding RNAs that interact with messenger RNAs (mRNAs) to post transcriptionally regulate protein translation. The miRs important in regulating skeletal muscle insulin resistance are not fully identified.PurposeThe purpose of this study was to determine the role of miR‐26a on lipid induced insulin resistance in skeletal muscle cells.MethodsC2C12 mouse skeletal muscle cells were treated to increase levels of miR‐26a (mimic) using commercially available kits (Qiagen). C2C12 mouse myoblasts were grown to full confluence, serum starved for 3 hours then treated with 0.5 mM palmitic acid (PA) to induce insulin resistance. Cells received PA for 24 hours followed by a 100 nM insulin treatment for 15 minutes. Real‐time PCR was used to examine levels of miR‐26a, and Western blotting was utilized to investigate insulin sensitive protein expression.ResultsCells receiving mimic had increases in miR‐26a levels and cells receiving palmitic acid had decreased responsiveness to insulin. Overexpressing miR‐26a levels in C2C12 muscle cells improved responsiveness to insulin in the presence of palmitic acid.ConclusionsHere we show that increasing miR‐26a levels in vitro can improve insulin responsiveness in mouse skeletal muscle cells with lipid induced insulin resistance. The mechanisms of how miR‐26a is operating in skeletal muscle need to be further explored.Support or Funding InformationFaculty Research GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.