Biochemical adaptations in white adipose tissue following aerobic exercise: from mitochondrial biogenesis to browning

2020 ◽  
Vol 477 (6) ◽  
pp. 1061-1081 ◽  
Author(s):  
Greg L. McKie ◽  
David C. Wright
Keyword(s):  
Adipose Tissue ◽  
Aerobic Exercise ◽  
White Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Past Research ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Underlying Mechanisms ◽  
Exercise Induced ◽  
A Site

Our understanding of white adipose tissue (WAT) biochemistry has evolved over the last few decades and it is now clear that WAT is not simply a site of energy storage, but rather a pliable endocrine organ demonstrating dynamic responsiveness to the effects of aerobic exercise. Similar to its established effects in skeletal muscle, aerobic exercise induces many biochemical adaptations in WAT including mitochondrial biogenesis and browning. While past research has focused on the regulation of these biochemical processes, there has been renewed interest as of late given the potential of harnessing WAT mitochondrial biogenesis and browning to treat obesity and type II diabetes. Unfortunately, despite increasing evidence that innumerable factors, both exercise induced and pharmacological, can elicit these biochemical adaptations in WAT, the underlying mechanisms remain poorly defined. Here, we begin with a historical account of our understanding of WAT exercise biochemistry before presenting detailed evidence in favour of an up-to-date model by which aerobic exercise induces mitochondrial biogenesis and browning in WAT. Specifically, we discuss how aerobic exercise induces increases in WAT lipolysis and re-esterification and how this could be a trigger that activates the cellular energy sensor 5′ AMP-activated protein kinase to mediate the induction of mitochondrial biogenesis and browning via the transcriptional co-activator peroxisome proliferator-activated receptor gamma co-activator-1 alpha. While this review primarily focuses on mechanistic results from rodent studies special attention is given to the translation of these results, or lack thereof, to human physiology.

Metabolic and cellular plasticity in white adipose tissue II: role of peroxisome proliferator-activated receptor-α

2005 ◽  
Vol 289 (4) ◽  
pp. E617-E626 ◽  
Author(s):  
Pipeng Li ◽  
Zhengxian Zhu ◽  
Yuyan Lu ◽  
James G. Granneman
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
White Adipose Tissue ◽  
Mitochondrial Biogenesis ◽  
Gene Profiling ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cl 316,243

Chronic activation of adipocyte β-adrenergic receptors induces remodeling of white adipose tissue (WAT) that includes a transient inflammatory response followed by mitochondrial biogenesis, induction of fatty acid oxidation genes, and elevation of tissue oxidative metabolism. Gene profiling experiments of WAT during remodeling induced by the β3-adrenergic receptor agonist CL-316,243 (CL) suggested that peroxisome proliferator-activated receptor-α (Ppara), which is upregulated by CL, might be an important transcriptional regulator of that process. Histological, physiological, and molecular analysis of CL-induced remodeling in wild-type mice and mice lacking Ppara demonstrated that Ppara was important for inducing adipocyte mitochondrial biogenesis and upregulating genes involved in fatty acid oxidation. Furthermore, Ppara-deficient mice exhibited sustained WAT inflammation during CL treatment, indicating that upregulation of Ppara limits proinflammatory signaling during chronic lipolytic activation. Together, these data support the hypothesis that WAT remodeling is an adaptive response to excessive fatty acid mobilization whereby Ppara and its downstream targets elevate fatty acid catabolism and suppress proinflammatory signaling.

scholarly journals Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue

2021 ◽  
Vol 22 (11) ◽  
pp. 6025
Author(s):  
Masaki Kobayashi ◽  
Yusuke Deguchi ◽  
Yuka Nozaki ◽  
Yoshikazu Higami
Keyword(s):  
Adipose Tissue ◽  
Caloric Restriction ◽  
White Adipose Tissue ◽  
Mitochondrial Gene ◽  
Energy Resource ◽  
Peroxisome Proliferator ◽  
Physiological Changes ◽  
Mitochondrial Gene Expression ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes

Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) regulates mitochondrial DNA replication and mitochondrial gene expression by interacting with several transcription factors. White adipose tissue (WAT) mainly comprises adipocytes that store triglycerides as an energy resource and secrete adipokines. The characteristics of WAT vary in response to systemic and chronic metabolic alterations, including obesity or caloric restriction. Despite a small amount of mitochondria in white adipocytes, accumulated evidence suggests that mitochondria are strongly related to adipocyte-specific functions, such as adipogenesis and lipogenesis, as well as oxidative metabolism for energy supply. Therefore, PGC-1α is expected to play an important role in WAT. In this review, we provide an overview of the involvement of mitochondria and PGC-1α with obesity- and caloric restriction-related physiological changes in adipocytes and WAT.

The Effect of Aerobic Exercise on Deteriorating VO2max and Diminished Mitochondrial Biogenesis During Aging

2021 ◽  
Vol 15 (12) ◽  
pp. 3462-3466
Author(s):  
Eda Akkiz Ağaşcioğlu ◽  
Ofcan Oflaz
Keyword(s):  
Aerobic Exercise ◽  
Mitochondrial Biogenesis ◽  
Vital Capacity ◽  
Antioxidant Activities ◽  
Reduction Rate ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Physiological Level ◽  
Cellular Environment ◽  
Age Related

Aging seems to be inevitable and gradual loss of physical activity is associated with frailty and many age-related disorders. Exercise is the way of keeping a healthy life and delaying aging process. Deterioration in pulmonary vital capacity is inevitable, and mitochondrial biogenesis also diminishes with aging. Regular aerobic exercise alleviates the diminishing vital capacity while increasing mitochondrial biogenesis in aging. Peroxisome proliferator-activated receptor c coactivator 1 alpha (PGC-1a), which is the master regulator of mitochondrial biogenesis, is activated by reactive oxygen species (ROS). Exercise-induced lactate leads to formation of ROS and synthesis of nitric oxide (NO) at physiological level. PGC1a regulation by NO seems to be controversial. Over the physiological limit of ROS and NO has toxic effects in cellular environment with reduced antioxidant activities in aging. Overall, exercise seems to be beneficial option to alleviate reduction rate of vital capacity and to enhance mitochondrial biogenesis via lactate-induced ROS formation. Keywords: Aging, Exercise, Maximum oxygen consumption rate, Lungs vital capacity, Mitochondria Biogenesis.

scholarly journals Trans-10, cis-12 conjugated linoleic acid causes inflammation and delipidation of white adipose tissue in mice: a microarray and histological analysis

2006 ◽  
Vol 27 (3) ◽  
pp. 282-294 ◽  
Author(s):  
P. Christopher LaRosa ◽  
Jess Miner ◽  
Yuannan Xia ◽  
You Zhou ◽  
Steve Kachman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
White Adipose Tissue ◽  
Binding Protein ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Functional Responses ◽  
Peroxisome Proliferator Activated Receptor ◽  
Transcript Levels

A combined histological and microarray analysis of the white adipose tissue (WAT) of mice fed trans-10, cis-12 conjugated linoleic acid (t10c12 CLA) was performed to better define functional responses. Mice fed t10c12 CLA for 14 days lost 85% of WAT mass, 95% of adipocyte lipid droplet volume, and 15 or 47% of the number of adipocytes and total cells, respectively. Microarray profiling of replicated pools ( n = 2 per day × diet) of control and treated mice ( n = 140) at seven time points after 1–17 days of t10c12 CLA feeding found between 2,682 and 4,216 transcript levels changed by twofold or more. Transcript levels for genes involved in glucose and fatty acid import or biosynthesis were significantly reduced. Highly expressed transcripts for lipases were significantly reduced but still abundant. Increased levels of mRNAs for two key thermogenesis proteins, uncoupling protein 1 and carnitine palmitoyltransferase 1, may have increased energy expenditures. Significant reductions of mRNAs for major adipocyte regulatory factors, including peroxisome proliferator activated receptor-γ, sterol regulatory binding protein 1, CAAT/enhancer binding protein-α, and lipin 1 were correlated with the reduced transcript levels for key metabolic pathways in the WAT. A prolific inflammation response was indicated by the 2- to 100-fold induction of many cytokine transcripts, including those for IL-6, IL-1β, TNF ligands, and CXC family members, and an increased density of macrophages. The mRNA changes suggest that a combination of cell loss, increased energy expenditure, and residual transport of lipids out of the adipocytes may account for the cumulative mass loss observed.

Effect of nitric oxide synthase inhibition on mitochondrial biogenesis in rat skeletal muscle

2007 ◽  
Vol 102 (1) ◽  
pp. 314-320 ◽  
Author(s):  
G. D. Wadley ◽  
G. K. McConell
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Mitochondrial Biogenesis ◽  
Acute Exercise ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Exercise Induced ◽  
Edl Muscle ◽  
Oxide Synthase

The purpose of this study was to determine whether nitric oxide synthase (NOS) inhibition decreased basal and exercise-induced skeletal muscle mitochondrial biogenesis. Male Sprague-Dawley rats were assigned to one of four treatment groups: NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME, ingested for 2 days in drinking water, 1 mg/ml) followed by acute exercise, no l-NAME ingestion and acute exercise, rest plus l-NAME, and rest without l-NAME. The exercised rats ran on a treadmill for 53 ± 2 min and were then killed 4 h later. NOS inhibition significantly ( P < 0.05; main effect) decreased basal peroxisome proliferator-activated receptor-γ coactivator 1β (PGC-1β) mRNA levels and tended ( P = 0.08) to decrease mtTFA mRNA levels in the soleus, but not the extensor digitorum longus (EDL) muscle. This coincided with significantly reduced basal levels of cytochrome c oxidase (COX) I and COX IV mRNA, COX IV protein and COX enzyme activity following NOS inhibition in the soleus, but not the EDL muscle. NOS inhibition had no effect on citrate synthase or β-hydroxyacyl CoA dehydrogenase activity, or cytochrome c protein abundance in the soleus or EDL. NOS inhibition did not reduce the exercise-induced increase in peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) mRNA in the soleus or EDL. In conclusion, inhibition of NOS appears to decrease some aspects of the mitochondrial respiratory chain in the soleus under basal conditions, but does not attenuate exercise-induced mitochondrial biogenesis in the soleus or in the EDL.

scholarly journals Current Progress in Adipose Tissue Biology: Implications in Obesity and Its Comorbidities

2020 ◽  
Vol 12 (2) ◽  
pp. 85-101
Author(s):  
Anna Meiliana ◽  
Nurrani Mustika Dewi ◽  
Andi Wijaya
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Uncoupling Protein ◽  
Common Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Brown Adipose ◽  
Key Factor ◽  
Beige Fat

BACKGROUND: Obesity has been decades become a highly interest study, accompanied by the realization that adipose tissue (AT) plays a major role in the regulation of metabolic function.CONTENT: In past few years, adipocytes classification, development, and differentiation has been significant changes. The white adipose tissue (WAT) can transform to a phenotype like brown adipose (BAT) type and function. Exercise and cold induction were the most common factor for fat browning; however batokines such as fibroblast growth factor (FGF)-21, interleukin (IL)-6, Slit homolog 2 protein (SLIT2)-C, and Meteorin-like protein (METRNL) perform a beneficial browning action by increasing peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α protein levels, a key factor to stimulate mitochondrial biogenesis and uncoupling Protein 1 (UCP1) transcription, thus change the WAT phenotype into beige.SUMMARY: AT recently known as a complex organ, not only bearing a storage function but as well as the master regulator of energy balance and nutritional homeostasis; brown and beige fat express constitutively high levels of thermogenic genes and raise our expectation on new strategies for fighting obesity and metabolic disorders.KEYWORDS: obesity, white adipose tissue, brown adipose tissue, beige adipose tissue, inflammation, IR, metabolic disease

scholarly journals Regulation of Peroxisome Proliferator-Activated Receptor Pathway During Torpor in the Garden Dormouse, Eliomys quercinus

2020 ◽  
Vol 11 ◽  
Author(s):  
Alexander J. Watts ◽  
Samantha M. Logan ◽  
Anna Kübber-Heiss ◽  
Annika Posautz ◽  
Gabrielle Stalder ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
White Adipose Tissue ◽  
Binding Activity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dna Binding Activity ◽  
Garden Dormouse ◽  
Eliomys Quercinus

Differential levels of n-6 and n-3 essential polyunsaturated fatty acids (PUFAs) are incorporated into the hibernator’s diet in the fall season preceding prolonged, multi-days bouts of torpor, known as hibernation. Peroxisome proliferator-activated receptor (PPAR) transcriptional activators bind lipids and regulate genes involved in fatty acid transport, beta-oxidation, ketogenesis, and insulin sensitivity; essential processes for survival during torpor. Thus, the DNA-binding activity of PPARα, PPARδ, PPARγ, as well as the levels of PPARγ coactivator 1α (PGC-1α) and L-fatty acid binding protein (L-FABP) were investigated in the hibernating garden dormouse (Eliomys quercinus). We found that dormice were hibernating in a similar way regardless of the n-6/n-3 PUFA diets fed to the animals during the fattening phase prior to hibernation. Further, metabolic rates and body mass loss during hibernation did not differ between dietary groups, despite marked differences in fatty acid profiles observed in white adipose tissue prior and at mid-hibernation. Overall, maintenance of PPAR DNA-binding activity was observed during torpor, and across three n-6/n-3 ratios, suggesting alternate mechanisms for the prioritization of lipid catabolism during torpor. Additionally, while no change was seen in L-FABP, significantly altered levels of PGC-1α were observed within the white adipose tissue and likely contributes to enhanced lipid metabolism when the diet favors n-6 PUFAs, i.e., high n-6/n-3 ratio, in both the torpid and euthermic state. Altogether, the maintenance of lipid metabolism during torpor makes it likely that consistent activity or levels of the investigated proteins are in aid of this metabolic profile.

scholarly journals Unripe Rubus coreanus Miquel Extract Containing Ellagic Acid Promotes Lipolysis and Thermogenesis In Vitro and In Vivo

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5954
Author(s):  
Kyeong Jo Kim ◽  
Eui-Seon Jeong ◽  
Ki Hoon Lee ◽  
Ju-Ryun Na ◽  
Soyi Park ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Ellagic Acid ◽  
Uncoupling Protein ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rubus Coreanus ◽  
Associated Proteins

Previously, we demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) and ellagic acid has hypocholesterolemic and antiobesity activity, at least partially mediated by the downregulation of adipogenic and lipogenic gene expression in high-fat diet (HFD)-fed animals. The present study investigated the thermogenic and lipolytic antiobesity effects of 5-uRCK and ellagic acid in HFD-induced obese C57BL/6 mice and explored its mechanism of action. Mice fed an HFD received 5-uRCK or ellagic acid as a post-treatment or pretreatment. Both post-treated and pretreated mice showed significant reductions in body weight and adipose tissue mass compared to the HFD-fed mice. The protein levels of lipolysis-associated proteins, such as adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and perilipin1 (PLIN1), were significantly increased in both the 5-uRCK- and ellagic acid-treated mouse epididymal white adipose tissue (eWAT). Additionally, thermogenesis-associated proteins, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase-1 (CPT1), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), in inguinal white adipose tissue (ingWAT) were clearly increased in both the 5-uRCK- and ellagic acid-treated mice compared to HFD-fed mice. These results suggest that 5-uRCK and ellagic acid are effective for suppressing body weight gain and enhancing the lipid profile.

scholarly journals Adipogenic role of alternatively activated macrophages in β-adrenergic remodeling of white adipose tissue

2016 ◽  
Vol 310 (1) ◽  
pp. R55-R65 ◽  
Author(s):  
Yun-Hee Lee ◽  
Sang-Nam Kim ◽  
Hyun-Jung Kwon ◽  
Krishna Rao Maddipati ◽  
James G. Granneman
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
De Novo ◽  
Flow Cytometric Analysis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Physical Relationship ◽  
Alternatively Activated Macrophages

De novo brown adipogenesis involves the proliferation and differentiation of progenitors, yet the mechanisms that guide these events in vivo are poorly understood. We previously demonstrated that treatment with a β3-adrenergic receptor (ADRB3) agonist triggers brown/beige adipogenesis in gonadal white adipose tissue following adipocyte death and clearance by tissue macrophages. The close physical relationship between adipocyte progenitors and tissue macrophages suggested that the macrophages that clear dying adipocytes might generate proadipogenic factors. Flow cytometric analysis of macrophages from mice treated with CL 316,243 identified a subpopulation that contained elevated lipid and expressed CD44. Lipidomic analysis of fluorescence-activated cell sorting-isolated macrophages demonstrated that CD44+ macrophages contained four- to five-fold higher levels of the endogenous peroxisome-proliferator activated receptor gamma (PPARγ) ligands 9-hydroxyoctadecadienoic acid (HODE), and 13-HODE compared with CD44− macrophages. Gene expression profiling and immunohistochemistry demonstrated that ADRB3 agonist treatment upregulated expression of ALOX15, the lipoxygenase responsible for generating 9-HODE and 13-HODE. Using an in vitro model of adipocyte efferocytosis, we found that IL-4-primed tissue macrophages accumulated lipid from dying fat cells and upregulated expression of Alox15. Furthermore, treatment of differentiating adipocytes with 9-HODE and 13-HODE potentiated brown/beige adipogenesis. Collectively, these data indicate that noninflammatory removal of adipocyte remnants and coordinated generation of PPARγ ligands by M2 macrophages provides localized adipogenic signals to support de novo brown/beige adipogenesis.

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