Decreased white fat cell thermogenesis in obese individuals

Böttcher, Hartfried; Fürst, Peter

doi:10.1038/sj.ijo.0800425

Cited by 41 publications

(32 citation statements)

References 32 publications

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“…Onset of obesity in ob/ob mice is associated with downregulation of genes coding for mitochondrial proteins [36], and heat production by white adipose tissue cells from obese humans is lower than in lean individuals [49]. All these findings are compatible with the hypothesis that changes in fuel partitioning and reduced oxidation of lipids in white adipocytes contribute to the development of obesity and type 2 diabetes.…”

Section: Discussionsupporting

confidence: 79%

Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce β-oxidation in white fat

et al. 2005

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Aims/hypothesis: Intake of n-3 polyunsaturated fatty acids reduces adipose tissue mass, preferentially in the abdomen. The more pronounced effect of marine-derived eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on adiposity, compared with their precursor α-linolenic acid, may be mediated by changes in gene expression and metabolism in white fat. Methods: The effects of EPA/ DHA concentrate (6% EPA, 51% DHA) admixed to form two types of high-fat diet were studied in C57BL/6J mice. Oligonucleotide microarrays, cDNA PCR subtraction and quantitative real-time RT-PCR were used to characterise gene expression. Mitochondrial proteins were quantified using immunoblots. Fatty acid oxidation and synthesis were measured in adipose tissue fragments. Results: Expression screens revealed upregulation of genes for mitochondrial proteins, predominantly in epididymal fat when EPA/DHA concentrate was admixed to a semisynthetic high-fat diet rich in α-linolenic acid. This was associated with a threefold stimulation of the expression of genes encoding regulatory factors for mitochondrial biogenesis and oxidative metabolism (peroxisome proliferator-activated receptor gamma coactivator 1 alpha [Ppargc1a, also known as Pgc1α] and nuclear respiratory factor-1 [Nrf1] respectively). Expression of genes for carnitine palmitoyltransferase 1A and fatty acid oxidation was increased in epididymal but not subcutaneous fat. In the former depot, lipogenesis was depressed. Similar changes in adipose gene expression were detected after replacement of as little as 15% of lipids in the composite highfat diet with EPA/DHA concentrate, while the development of obesity was reduced. The expression of Ppargc1a and Nrf1 was also stimulated by n-3 polyunsaturated fatty acids in 3T3-L1 cells. Conclusions/interpretation: The antiadipogenic effect of EPA/DHA may involve a metabolic switch in adipocytes that includes enhancement of β-oxidation and upregulation of mitochondrial biogenesis.

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Section: Discussionsupporting

confidence: 79%

Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce β-oxidation in white fat

et al. 2005

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“…However, the effect on energy balance may be relatively small, since white fat contributes to the resting metabolic rate in humans by only about 5%. 38 On the other hand, a decrease in ATP synthesis due to respiratory uncoupling in white fat with a consequent rise in ADP and AMP levels may result in allosteric regulations of key enzymes of carbohydrate and lipid metabolism. Based on its function during adaptive thermogenesis in adipocytes of the brown fat, UCP1 is the only homologue with a proven uncoupling activity.…”

Section: Role Of Ucps In White Adipose Tissuementioning

confidence: 99%

Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores

et al. 2004

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As indicated by in vitro studies, both lipogenesis and lipolysis in adipocytes depend on the cellular ATP levels. Ectopic expression of mitochondrial uncoupling protein 1 (UCP1) in the white adipose tissue of the aP2-Ucp1 transgenic mice reduced obesity induced by genetic or dietary manipulations. Furthermore, respiratory uncoupling lowered the cellular energy charge in adipocytes, while the synthesis of fatty acids (FA) was inhibited and their oxidation increased. Importantly, the complex metabolic changes triggered by ectopic UCP1 were associated with the activation of AMP-activated protein kinase (AMPK), a metabolic master switch, in adipocytes. Effects of several typical treatments that reduce adiposity, such as administration of leptin, b-adrenoceptor agonists, bezafibrate, dietary n-3 polyunsaturated FA or fasting, can be compared with a phenotype of the aP2-Ucp1 mice. These situations generally lead to the upregulation of mitochondrial UCPs and suppression of the cellular energy charge and FA synthesis in adipocytes. On the other hand, FA oxidation is increased. Moreover, it has been shown that AMPK in adipocytes can be activated by adipocyte-derived hormones leptin and adiponectin, and also by insulin-sensitizes thiazolidinediones. Thus, it is evident that metabolism of adipose tissue itself is important for the control of body fat content and that the cellular energy charge and AMPK are involved in the control of lipid metabolism in adipocytes. The reciprocal link between synthesis and oxidation of FA in adipocytes represents a prospective target for the new treatment strategies aimed at reducing obesity.

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“…In a long-term basis, FAO stimulation would probably help to diminish insulin resistance in peripheral tissues (less ectopic fat accumulation) and boost metabolic rate and weight loss. Indeed, many evidences corroborate that efficient mitochondrial WAT FAO may increase respiratory capacity, reduce adipocyte size, enhance lipolysis and reduce lipotoxicity [17,87,88]. Unpublished data from our group show that an increase on mitochondrial WAT FAO (30%) and WAT oxygen consumption (10%) due to the action of unsaturated fatty acid treatment (palmitoleic acid) occurs simultaneously to an augmentation on lipolysis (3,5-fold).…”

Section: Mitoneet Inhibitionmentioning

confidence: 62%

“…Accordingly, liver receptor X activation in vivo and in vitro led to decreased adipocyte size in WAT and increased glycerol release from primary adipocytes, respectively, with a concomitant increase in oxygen consumption rates [87]. Therefore, liver receptor X is another candidate to modulate WAT energy expenditure.…”

Section: Liver Receptor Xmentioning

confidence: 99%

“…Recently, a WAT knockout mouse for liver receptor X (ATaKO mouse) was generated and it presented more weight gain and fat mass on a high fat diet compared with wild-type controls, as a result of the decrease in WAT lipolytic and oxidative capacities [87]. Accordingly, liver receptor X activation in vivo and in vitro led to decreased adipocyte size in WAT and increased glycerol release from primary adipocytes, respectively, with a concomitant increase in oxygen consumption rates [87].…”

Section: Liver Receptor Xmentioning

confidence: 99%

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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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Decreased white fat cell thermogenesis in obese individuals

Cited by 41 publications

References 32 publications

Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce β-oxidation in white fat

Polyunsaturated fatty acids of marine origin upregulate mitochondrial biogenesis and induce β-oxidation in white fat

Role of energy charge and AMP-activated protein kinase in adipocytes in the control of body fat stores

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

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