Anti-catabolic effects of conjugated linoleic acid and omega-3 polyunsaturated fatty acid administration in resting or loaded skeletal muscles of middle aged mice during 20 weeks of high fat diet.

摘要

The age-related loss of muscle mass and strength (i.e. sarcopenia) is a fundamental cause of frailty, functional decline, and disability, leading to poor quality of life in aging populations. Sarcopenic obesity, a recent medical term, refers to a new trend in aged individuals who simultaneously demonstrate reductions and increases in lean mass and fat mass, respectively. It is currently thought that increases in fat mass with age start the actual sarcopenic process by increasing inflammatory factors. Chronic resistance exercise training (RET) is considered the most cost effective intervention to combat sarcopenia, improving muscle strength followed by improved quality of life. Conjugated linoleic acid (CLA) and omega-3 polyunsaturated fatty acid (n-3) attract great attention for their anti-inflammatory properties, possibly reducing risks of muscle wasting. However, the efficacy of CLA/n-3 on resting or loaded muscles during chronic high fat diet (HFD)-induced inflammation has not been fully elucidated. Therefore, the overarching aim of the present study was to investigate the impact of HFD-induced inflammation on sarcopenia and the effects of 20-wk CLA/n-3 administration on muscle at rest or with RET in the middle aged mice. Nine-month old C57BL/6 male mice were randomly assigned to five groups (n=10/group): 1) normal diet (C), 2) High fat diet (H), 3) HFD+RET (HE), 4) HFD+CLA/n-3 (HCN), and 5) HFD+RET+CLA/n-3 (HECN). Progressive RET (4 sets of 3 repetitions with 1-min inter-set rest) was conducted using a ladder climbing device 3x/wk for 20 wks. The combined supplement was comprised of 1% CLA (0.5% of c9, t11 and 0.5% of t10, c12) and 1% n-3. Body composition (dual X-ray absorptiometry, DXA), grip strength, and sensorimotor function were assessed pre- and post-experiment. Muscle isolation was performed to determine muscle wet weight and RT-PCR was used to analyze transcript levels of target factors involved in muscle cell growth and regeneration: pro-inflammatory regulators [tumor necrosis factor alpha (TNF-alpha) and Interleukin-1 beta (IL-1beta)], anti-inflammatory regulators (IL-6 and IL-15), protein kinase B (Akt), mammalian target of rapamycin (mTOR), atrogin-1, muscle ring finger 1 (MURF1), insulin-like growth factor-I Ea(IGF-IEa), MyoD, and myogenin. There were significant group x time interactions (p ≤ 0.01) for lean body mass (LBM), fat mass (FM), grip strength, and sensorimotor function. FM increased in H (+74%) and HE (+142%), (p ≤ 0.01) and HECN (+43%, p ≤ 0.01) but not in C and HCN. LBM decreased in C (-27%), H (-31%), and HE (-55%), (p ≤ 0.01) while no change was found in HECN. Strength significantly declined in H (-15%) and HCN (-17%), (p ≤ 0.01) but was maintained in C. Sensorimotor function markedly declined in H (-11%, p ≤ 0.01) with no change in C, HCN, and HE. Interestingly, CLA/n-3 administration appeared to facilitate greater RET-mediated improvements in strength (+22%) and sensorimotor coordination (+17%, p ≤ 0.01). There were significant group effects in muscle wet weight. Gastrocnemius wet weight significantly decreased in C (-27%), H (-39%) and HCN (-35%), (p ≤ 0.01) from baseline but was maintained in HE and HECN. Soleus wet weight significantly decreased in H (-24%, p ≤ 0.01) while maintained in C, HE, and HCN. In contrast, soleus wet weight was greater in HECN (p ≤ 0.01) compared to C, H, and HCN. FA was significantly decreased in HECN (-22%, p ≤ 0.05). While eigen (lambda) 2 decreased in HECN (-8%, p ≤ 0.05), HCN significantly increased lambda3 from baseline (+16%, p ≤ 0.05). Chronic CLA/n-3 administration improved the inflammatory state in HFD-fed middle aged animals. TNF-alpha mRNA expression was greater in H compared to C, HCN, HECN (p ≤ 0.05) and HE (p ≤ 0.01) in the gastrocnemius. Moreover, HE, HCN, and HECN demonstrated increased IL-6 mRNA expression (p ≤ 0.05) from baseline in the gastrocnemius. HCN showed increased IL-15 mRNA expression (p ≤ 0.01) from baseline and was greater than H (p ≤ 0.05) in the gastrocnemius. Both H and HE had significantly lower IL-15 expression than C (p ≤ 0.01) and HECN (p ≤ 0.05) in the soleus. Based on our findings, chronic HFD negatively altered body composition, muscle wet weight, and functional capacity in middle aged mice. Daily CLA/n-3 administration attenuated these impairments while facilitating RET-induced improvement in functional capacity, possibly by improving the inflammatory state. Future research needs to apply for a human trial in the same condition to authenticate our findings.