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      The effects of exercise and cold exposure on mitochondrial biogenesis in skeletal muscle and white adipose tissue

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          Abstract

          [Purpose]

          The purpose of this study was to determine whether exercise or/and cold exposure regulate mitochondria biogenesis-related gene expression in soleus and inguinal adipose tissue of mice.

          [Methods]

          Forty ICR 5-week old male mice were divided into four groups: thermoneutrality-untrained (23 ± 1 °C in room temperature, n=10), cold-water immersion (24 ± 1 °C, n=10), exercise in neutral temperature (34 ± 1 °C, n=10), and exercise in cold temperature (24 ± 1 °C, n=10). The mice performed swimming exercise (30 min to 60 min, 5 times) for 8 weeks. After 8 weeks, we confirmed mitochondrial biogenesis-related gene expression changes for peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), nuclear respiratory factors 1 (NRF1), and mitochondrial transcription factor A (Tfam) in soleus muscle and inguinal adipose tissue, and the related protein expression in soleus muscle.

          [Results]

          In soleus muscle, PGC-1α expression significantly increased in response to cold exposure (p = 0.006) and exercise (p = 0.05). There was also significant interaction between exercise and cold exposure (p = 0.005). Only exercise had a significant effect on NRF1 relative expression (p=0.001). Neither cold exposure nor the interaction showed significant effects (p = 0.1222 and p = 0.875, respectively). Relative Tfam expression did not show any significant effect from exercise. In inguinal adipose tissue, relative PGC-1α expression did not significantly change in any group. NRF1 expression showed a significant change from exercise (p = 0.01) and cold exposure (p = 0.011). There was also a significant interaction between exercise and cold exposure (p = 0.000). Tfam mRNA expression showed a significant effect from exercise (p=0.000) and an interaction between exercise and cold exposure (p=0.001). Only temperature significantly affected PGC-1α protein levels (p=0.045). Neither exercise nor the interaction were significant (p = 0.397 and p = 0.292, respectively). NRF1 protein levels did not show a significant effect in any experimental treatments. Tfam protein levels showed a significant effect in the exercise group (p=0.012), but effects of neither cold exposure nor the interaction were significant (p = 0.085 and p=0.374, respectively).

          [Conclusion]

          Exercise and cold exposure promoted increased expression of mitochondrial biogenesis- related genes in soleus muscle. Only cold exposure had a significant effect on PGC-1α protein expression and only exercise had a significant effect on Tfam protein expression. In inguinal adipose tissue, there was interaction between exercise and cold exposure in expression of mitochondrial biogenesis-related genes.

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          Most cited references39

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          Brown adipose tissue: function and physiological significance.

          The function of brown adipose tissue is to transfer energy from food into heat; physiologically, both the heat produced and the resulting decrease in metabolic efficiency can be of significance. Both the acute activity of the tissue, i.e., the heat production, and the recruitment process in the tissue (that results in a higher thermogenic capacity) are under the control of norepinephrine released from sympathetic nerves. In thermoregulatory thermogenesis, brown adipose tissue is essential for classical nonshivering thermogenesis (this phenomenon does not exist in the absence of functional brown adipose tissue), as well as for the cold acclimation-recruited norepinephrine-induced thermogenesis. Heat production from brown adipose tissue is activated whenever the organism is in need of extra heat, e.g., postnatally, during entry into a febrile state, and during arousal from hibernation, and the rate of thermogenesis is centrally controlled via a pathway initiated in the hypothalamus. Feeding as such also results in activation of brown adipose tissue; a series of diets, apparently all characterized by being low in protein, result in a leptin-dependent recruitment of the tissue; this metaboloregulatory thermogenesis is also under hypothalamic control. When the tissue is active, high amounts of lipids and glucose are combusted in the tissue. The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.
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            Regulation of mitochondrial biogenesis.

            Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer's disease. PGC-1alpha (peroxisome-proliferator-activated receptor gamma co-activator-1alpha) is a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1alpha itself is regulated by several different key factors involved in mitochondrial biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial biogenesis and function may provide potentially important novel therapeutic targets.
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              Tracking adipogenesis during white adipose tissue development, expansion and regeneration.

              White adipose tissue displays high plasticity. We developed a system for the inducible, permanent labeling of mature adipocytes that we called the AdipoChaser mouse. We monitored adipogenesis during development, high-fat diet (HFD) feeding and cold exposure. During cold-induced 'browning' of subcutaneous fat, most 'beige' adipocytes stem from de novo-differentiated adipocytes. During HFD feeding, epididymal fat initiates adipogenesis after 4 weeks, whereas subcutaneous fat undergoes hypertrophy for a period of up to 12 weeks. Gonadal fat develops postnatally, whereas subcutaneous fat develops between embryonic days 14 and 18. Our results highlight the extensive differences in adipogenic potential in various fat depots.
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                Author and article information

                Journal
                J Exerc Nutrition Biochem
                J Exerc Nutrition Biochem
                JENB
                Journal of Exercise Nutrition & Biochemistry
                한국운동영양학회
                2233-6834
                2233-6842
                30 June 2017
                30 June 2017
                : 21
                : 2
                : 39-47
                Affiliations
                [1. ]Physical Activity & Performance Institute (PAPI), Konkuk University, Seoul Republic of Korea
                [2. ]Department of Physical Education, Korea University, Seoul Republic of Korea
                [3. ]Department of Physical Education, Konkuk University, Seoul Republic of Korea
                Author notes
                *Kiwon Lim Department of Physical Education, Konkuk University, Seoul, Republic of Korea. Tel : +82-2-450-3827 Email : exercise@ 123456konkuk.ac.kr
                Article
                JENB_2017_v21n2_39
                10.20463/jenb.2017.0020
                5545200
                28715885
                acbb1621-f25e-43ba-9112-993da03bfdc7
                ©2017 The Korean Society for Exercise Nutrition

                ©2017 Nana Chung et al.; Licensee Journal of Exercise Nutrition and Biochemistry. This is an open accessarticle distributed under the terms of the creative commons attribution license ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the orginal work is properly cited.

                History
                : 15 May 2017
                : 19 June 2017
                : 20 June 2017
                Funding
                Funded by: National Research Foundation of Korea
                Award ID: NRF NO.2014S1A5B5A01014504
                Categories
                Original Article

                exercise,cold exposure,pgc-1α,nrf-1,tfam,mitochondrial biogenesis

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