Adipose Fibroblast Growth Factor 21 Is Up-Regulated by Peroxisome Proliferator-Activated Receptor γ and Altered Metabolic States

Muise, Eric S.; Azzolina, B.; Kuo, David W; El-Sherbeini, Mohamed; Tan, Yi; Yuan, Xiling; Mu, James; Thompson, John R.; Berger, Joel P.; Wong, Kenny K.

doi:10.1124/mol.108.044826

Cited by 263 publications

(231 citation statements)

References 41 publications

(56 reference statements)

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“…In particular, in our review, we focused attention on FGF21, which is expressed mainly by the liver, but also by other tissues such as adipose tissue [31] . Moreover, adipose tissue showed a large high expression of FGF receptor 1 [32] and emerged as a strong candidate to represent a predominant FGF21 target tissue.…”

Section: Possible Role Of Fgf21 In Assessing the Degree Of Lipodystrophymentioning

confidence: 99%

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

Benedini

Luzi

2016

Journal of Translational Internal Medicine

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Recently new evidence about fibroblast growth factor 21 (FGF21) highlights the opportunities to use this molecule in new pharmaceutical formulations to combat type 2 diabetes and metabolic syndrome. It is well known that HIV is per se a condition of insulin resistance and in particular the patient with HIV-related lipodystrophy has a condition strictly related to metabolic syndrome. Lipodystrophy is associated with severe metabolic side effects, including dyslipidemia, hepatic insulin resistance, and lipid oxidation impairment. Research carried out showed that FGF21 levels were significantly increased in untreated HIV-1-infected patients and the increase was much marked in HIV-1-infected antiretroviral-treated patients that have developed lipodystrophy and in the patients with greatest metabolic alterations. FGF21 is expressed mainly by the liver, but also by other tissues such as the thymus, adipose tissue, and skeletal muscle. Therefore, many researchers have considered the investigation of possible variations of FGF21 in patients with significant alterations in body composition both in regard to fat mass and lean mass. In the light of the possible interactions between FGF21 and metabolic syndrome, it seems interesting to evaluate the implication of this hormone in patients with HIV-related lipodystrophy who have a severe metabolic picture of insulin resistance with important alterations in body composition.

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Section: Possible Role Of Fgf21 In Assessing the Degree Of Lipodystrophymentioning

confidence: 99%

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

Benedini

Luzi

2016

Journal of Translational Internal Medicine

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“…However, the physiological role of FGF21 is still not fully understood. Expression of FGF21 has predominantly been detected in liver and pancreatic tissues, but low levels are also present in muscle and fat (4,12,13,14). In human muscle tissue, insulin has been shown to upregulate FGF21 mRNA expression during a hyperinsulinemic euglycemic clamp (13).…”

Section: Introductionmentioning

confidence: 99%

Impact of short-term high-fat feeding and insulin-stimulated FGF21 levels in subjects with low birth weight and controls

Vienberg

Brøns²,

Nilsson³

et al. 2012

European Journal of Endocrinology

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ObjectiveFibroblast growth factor 21 (FGF21) is a metabolic factor involved in glucose and lipid metabolism. However, little is known about the physiological role of FGF21 during a dietary challenge in humans.Research design and methodsTwenty healthy low birth weight (LBW) with known risk of type 2 diabetes and 26 control (normal birth weight (NBW)) young men were subjected to 5 days of high-fat (HF) overfeeding (+50%). Basal and clamp insulin-stimulated serum FGF21 levels were examined before and after the diet, andFGF21mRNA expression was measured in muscle and fat biopsies respectively.ResultsFive days of HF overfeeding diet significantly (P<0.001) increased fasting serum FGF21 levels in both the groups (P<0.001). Furthermore, insulin infusion additionally increased serum FGF21 levels to a similar extent in both the groups. Basal mRNA expression ofFGF21in muscle was near the detection limit and not present in fat in both the groups before and after the dietary challenge. However, insulin significantly (P<0.001) increasedFGF21mRNA in both muscle and fat in both the groups during both diets.ConclusionShort-term HF overfeeding markedly increased serum FGF21 levels in healthy young men with and without LBW but failed to increase muscle or fatFGF21mRNA levels. This suggests that the liver may be responsible for the rise of serum FGF21 levels during overfeeding. In contrast, the increase in serum FGF21 levels during insulin infusion may arise from increased transcription in muscle and fat. We speculate that increased serum FGF21 levels during HF overfeeding may be a compensatory response to increase fatty acid oxidation and energy expenditure.

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“…In some PCOS cases, insulin resistance and hyperinsulinaemia play a role (3,4). Insulin resistance is related to excessive visceral fat distribution (5,6), as well as inflammation and hormonal disturbances related to adipose tissue (6,7). A recently discovered adipokine that may play a role in insulin resistance development is fibroblast growth factor 21 (FGF21) (8).…”

Section: Introductionmentioning

confidence: 99%

Circulating FGF21 levels are related to nutritional status and metabolic but not hormonal disturbances in polycystic ovary syndrome

Olszanecka-Glinianowicz¹,

Madej²,

Wdowczyk³

et al. 2015

European Journal of Endocrinology

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Objective: The aim of this study was to analyse relationships between plasma fibroblast growth factor 21 (FGF21) levels and nutritional status, and metabolic and hormonal disturbances in polycystic ovary syndrome (PCOS) women. Design and setting: A cross-sectional study involving 85 PCOS (48 obese) and 72 non-PCOS women (41 obese) was conducted to evaluate the relationship between FGF21 levels and PCOS. Methods: Anthropometric parameters and body composition were determined. In the fasting state; serum concentrations of glucose, androgens, FSH, LH, SHBG, insulin and FGF21 were measured. Results: Plasma FGF21 levels were significantly higher in obese women compared with normal-weight women in both PCOS and non-PCOS subgroups (120.3 (18.2-698) vs 62.3 (16.4-323.6) pg/ml, P!0.05 and 87.2 (12.9-748.4) vs 62.9 (18.0-378.8) pg/ml, P!0.05 respectively). Additionally, circulating FGF21 levels were significantly higher in the obese PCOS subgroup compared with the non-PCOS subgroup (120.3 (18.2-698.0) vs 87.2 (12.9-748.4) pg/ml, P!0.05). Circulating FGF21 levels were proportional to BMI (RZ0.27; P!0.001), body fat mass (RZ0.24; P!0.01) and percentage (RZ0.24; P!0.01), as well as waist circumference (RZ0.26; P!0.01). Additionally, plasma insulin and homeostasis model assessment of insulin resistance (HOMA-IR) values were related to FGF21 levels (RZ0.44; P!0.001 and RZ0.19; P!0.05 respectively). In multiple regression analysis, circulating FGF21 level variability was explained by HOMA-IR values and fat percentage, as well as waist circumference, but not correlated with oestradiol levels and free androgen index values. Conclusions: Higher circulating FGF21 levels are related to nutritional status and insulin resistance independent of PCOS. Increased FGF21 is associated with metabolic but not hormonal disturbances.

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Adipose Fibroblast Growth Factor 21 Is Up-Regulated by Peroxisome Proliferator-Activated Receptor γ and Altered Metabolic States

Cited by 263 publications

References 41 publications

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

Lipodystrophy HIV-related and FGF21: A new marker to follow the progression of lipodystrophy?

Impact of short-term high-fat feeding and insulin-stimulated FGF21 levels in subjects with low birth weight and controls

Circulating FGF21 levels are related to nutritional status and metabolic but not hormonal disturbances in polycystic ovary syndrome

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