R-α-Lipoic acid and acetyl-l-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes

Shen, Weili; Liu, K.; Tian, Chan; Yang, Lü; Li, X.; Ren, Jianke; Packer, Lester; Cotman, Carl W.; Liu, J.

doi:10.1007/s00125-007-0852-4

Cited by 98 publications

(82 citation statements)

References 44 publications

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“…Total DNA and mtDNA were extracted using the QIAamp DNA Mini Kit (Qiagen, Hilden, Germany), and quantitative PCR was done using 18S rRNA primers for a nuclear target sequence and primers for the mitochondrial D-loop as a mtDNA target (25).…”

Section: Mtdna Copy Numbermentioning

confidence: 99%

Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4‐week hindlimb unloading

et al. 2012

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SummaryMitochondrial dynamics is highly involved in muscle atrophy, the slow twitch muscle as soleus, preferentially affected by hindlimb unloading (HU), was well characterized by mitochondrial dysfunction in biogenesis. However, the fast twitch muscles like tibialis anterior (TA) and gastrocnemius (GAS), which are the most massive parts of the hindlimb muscles, are less elucidated on mitochondrial adaptations responding to HU. To investigate the mitochondrial dynamic responses and the involved molecules mediating atrophy in TA and GAS, we studied a 4-week HU mouse model. We found GAS was preferentially affected to atrophy by unloading compared with TA. Furthermore, the depressed mitochondrial biogenesis occurred, accounting for mitochondrial loss in GAS by unloading. PGC-1a, as well as its transcriptional/post-translational modification regulators, such as p-CREB, SIRT1, and p-AMPK, were consistently reduced in response to unloading in GAS. Molecules relevant to autophagy, mitochondrial fusion, and fission, were compromised following unloading both in TA and GAS. These results suggested that TA exhibited resistance to unloading induced muscle atrophy while GAS presented significant mitochondrial loss, which might be due to the mitochondrial biogenesis suppressed by the inactivation of PGC-1a. However, both in TA and GAS muscles, a similar sedentary mitochondrial dynamics of mitochondrial fusion and fission was induced by unloading though TA exhibited little muscle atrophy. IUBMBIUBMB Life, 64(11): 901-910, 2012

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Section: Mtdna Copy Numbermentioning

confidence: 99%

Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4‐week hindlimb unloading

et al. 2012

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“…Primer sequences used for quantification of mRNA by real-time quantitative PCR for PPARa, carnitine palmitoyltransferase I (CPT-1), and 18S ribosomal RNA and mRNA have been described previously (29) .…”

Section: Rna Isolation and Rt-pcr For Ppara And Carnitine Palmitoyltrmentioning

confidence: 99%

Mitochondrial dysfunction in the liver of type 2 diabetic Goto–Kakizaki rats: improvement by a combination of nutrients

et al. 2011

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Treatment with a combination of four nutrients, i.e. R-a-lipoic acid, acetyl-L-carnitine, nicotinamide and biotin, just as with pioglitazone, significantly improves glucose tolerance, insulin release, plasma NEFA, skeletal muscle mitochondrial biogenesis and oxidative stress in Goto -Kakizaki (GK) rats. However, it is not known whether treatment with these nutrients can improve mitochondrial function and reduce oxidative stress in GK rats. The effects of a combination of these four nutrients on mitochondrial function, oxidative stress and apoptosis in GK rat liver were investigated. Livers of untreated GK rats showed (1) abnormal changes in the activities of mitochondrial complexes (decreases in I, III and IV and increases in II and V), (2) increases in protein oxidation, (3) decreases in antioxidant enzymes (superoxide dismutase, glutathione S-transferase, NADH-quinone oxidoreductase-1), (4) a decrease in total antioxidant capacity but increases in reduced glutathione level and glyceraldehyde 3-phosphate dehydrogenase expression and (5) significant increases in apoptosis biomarkers, including expression of p21 and p53. A 3-month treatment with the four nutrients significantly improved most of these abnormalities in GK rats, and the effects of the nutrient combination were greater than those of pioglitazone for most of these indices. These results suggest that dietary supplementation with nutrients that are thought to influence mitochondrial function may be an effective strategy for improving liver dysfunction in GK diabetic rats.Key words: R-a-Lipoic acid: Acetyl-L-carnitine: Nicotinamide: Biotin: Oxidative damage: Phase II enzymes: Apoptosis Type 2 (non-insulin-dependent) diabetes mellitus is one of the most common metabolic diseases in humans, affecting about 3 % of the human population. Clinically, it is rather a group of related diseases, characterised by chronic hyperglycaemic levels, due to an impairment in the balance among the three processes of b-cell secretion of insulin, peripheral resistance to insulin and hepatic glucose production (1,2) . Depending on several factors, such as obesity, age of onset, mode of inheritance and severity of glucose intolerance, clinical features of individuals suffering from type 2 diabetes are highly variable.Despite being one of the most common non-communicable diseases in the world, the exact mechanism (or mechanisms) leading to glucose intolerance is still not clear (1,3) . Recently, mitochondrial dysfunction due to oxidative damage has become known as a major contributor to ageing, to degenerative diseases such as cancer, and to the metabolic syndrome, obesity and type 2 diabetes (4,5) . A group of antioxidants/ metabolites which can act to improve mitochondrial function and protect mitochondria from oxidative damage, when supplemented in the diet, have been defined as mitochondrial † These authors contributed equally to this work.

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“…3T3-L1 adipocytes exposed to the insulin sensitizer rosiglitazone, to β3-adrenergic receptor activation and to the combined use of R-α-lipoic acid and acetyl-L-carnitine displayed enhanced mitochondrial population, augmentation of the expression of several mitochondrial proteins and augmented FAO [49][50][51]. These findings were later proven in vivo by the use of white adipocytes from ob/ob mice treated with rosiglitazone that presented augmented mitochondrial mass, markedly enhanced oxygen consumption and significantly increased palmitate oxidation [17,19,52].…”

Section: Overview Of Mitochondrial Relevance In White Adipocytesmentioning

confidence: 99%

Mitochondrial Actions for Fat Browning and Energy Expenditure in White Adipose Tissue

Pbm¹,

Lopes²,

Alonso-Vale³

2016

Journal of Obesity and Overweight

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Obesity can be defined as the disruption in the balance between fuel intake and energy expenditure in favor of energy conservation. Together with type 2 diabetes (T2DM), these are the two of the most prevalent diseases affecting modern societies, arising mostly by changes in eating habits and a sedentary lifestyle associated with poorly known genetic determinants. Obesity predisposes to the so-called metabolic syndrome, which includes inflammation, hypertension, T2DM and cardiovascular diseases [1]. Obesity is imposing an increasingly heavy burden on the world's population in rich and poor nations alike, with almost 30 percent of people globally now either obese (BMI ≥ 30) or overweight (BMI ≥ 25) [2]. In fact, the number of overweight and obese people rose from 857 million in 1980 to 2.1 billion in 2013 [2]. Recently, obesity and metabolic syndrome were associated with mitochondrial dysfunction and deranged regulation of metabolic genes [3]. Interestingly, mitochondria of obese individuals seem to be different from those of lean individuals. Mitochondria from obese individuals display lower energy-generating capacity, less defined inner membranes and reduced fatty acid oxidation (FAO) [4]. AbstractWhite adipose tissue (WAT) is an endocrine organ with crucial role in the development of obesity and related diseases. White adipocytes have less mitochondria than brown adipocytes; nevertheless, there is an increasing body of evidence showing that mitochondrial parameters play a relevant role in WAT physiology, such as proliferation, differentiation and triacylglycerol storage levels. These parameters comprise mitochondria turnover, oxidative capacity, uncoupling, reactive oxygen species levels and oxygen consumption. In addition, the existence of beige (brown in white) adipose tissue and the transdifferatiation of WAT in brown adipose tissue are intrinsically related to mitochondria activity. Herein we highlight that the concerted action of stimulated lipolysis, mitochondrial oxidative metabolism and uncoupling (futile cycle) can enhance WAT energy expenditure. We consider WAT mitochondrial function a promising target for the development of therapies tackling lipotoxicity, obesity and related diseases. White adipose tissue (WAT) is the main tissue linked to obesity. WAT represents around 10% of total body weight in lean adults and more than 50% in obese individuals [5]. WAT is composed of mature adipocytes and the stromal-vascular fraction that contains preadipose cells (or adipoblasts), fibroblasts, immune cells, and blood vessel-associated cells [6]. A single and large lipid droplet occupies most of the white adipocyte volume and WAT copes with obesity either expanding (hypertrophy) or recruiting new cells (hyperplasia) [7]. WAT secretes an array of peptide hormones called adipokines (including leptin and adiponectin), which regulate neurological activities such as appetite and behavior, metabolic activities of peripheral tissues [8] and produce several pro-inflammatory cytokines, such as tumor necrosis factor alp...

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R-α-Lipoic acid and acetyl-l-carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes

Cited by 98 publications

References 44 publications

Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4‐week hindlimb unloading

Depressed mitochondrial biogenesis and dynamic remodeling in mouse tibialis anterior and gastrocnemius induced by 4‐week hindlimb unloading

Mitochondrial dysfunction in the liver of type 2 diabetic Goto–Kakizaki rats: improvement by a combination of nutrients

Mitochondrial Actions for Fat Browning and Energy Expenditure in White Adipose Tissue

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