Fibroblast growth factor 21 (FGF21) and bone: is there a relationship in humans?

Lee, P; Linderman, Joyce D.; Smith, Sarah; Brychta, Robert J.; Perron, Rachel M.; Idelson, Christopher; Werner, C.; Chen, Kong Y.; Celi, Francesco S.

doi:10.1007/s00198-013-2464-9

Cited by 50 publications

(41 citation statements)

References 19 publications

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“…25 A link between energy expenditure, metabolism, and bone mass certainly exists with adiponectin and endocrine FGFs potentially playing direct roles. 18, 41 Both increased FGF21 and adiponectin lead to bone loss in mice and adiponectin and thiazolidinedione drugs (which elevate adiponectin) are both linked to reduced bone mass and osteoporosis. 18, 21, 41 We found reduced FGF23 in APN-Tg mice and elevated levels in APN KO mice on normal chow, a result similar to one clinical study that found an inverse relationship between these hormones.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin alters renal calcium and phosphate excretion through regulation of klotho expression

Rutkowski

Pastor

Sun

et al. 2017

Kidney International

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The kidney controls systemic calcium and phosphate levels and disturbances of its control mechanisms can lead to a variety of diseases. The insulin-sensitizing adipokine adiponectin is renoprotective and accelerates functional recovery following renal injury. However, unlike other adipokines, adiponectin is reduced in obesity. High adiponectin levels are also correlated with bone loss, suggestive of an additional action in mineral metabolism. Using knockout, wildtype, and adiponectin overexpressing transgenic mice, we sought to identify the mechanistic basis for adiponectin’s ability to regulate calcium and phosphate balance at the level of the kidney. Adiponectin knockout mice exhibited lower serum calcium, lower urinary calcium excretion and markedly lower serum fibroblast growth factor 23 (FGF23) levels, although circulating klotho concentrations were significantly higher than in wildtype littermates. The transgenic mice exhibited lower bone mass and strength, particularly compared to adiponectin knockout mice. The transgenic mice were hyper-responsive to 2% phosphate-enriched diet, exhibiting 2-fold higher serum FGF23 and concomitantly higher fractional phosphate excretion. These mice also excreted more calcium with calcium-enriched diet and had less renal klotho protein expression. In contrast, the knockout mice exhibited a smaller increase in FGF23 and maintained elevated klotho levels on both mineral challenges. Kidney-specific adiponectin expression in doxycycline-inducible adiponectin mice and adiponectin addition in vitro confirmed adiponectin’s ability to reduce tubular epithelial cell klotho secretion. Thus, adiponectin alters calcium and phosphate balance and renal mineral excretion, in part, through klotho. This work highlights the profound effects of adipose tissue on renal function and has identified a new mechanism by which adiponectin may regulate bone mass.

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Section: Discussionmentioning

confidence: 99%

Adiponectin alters renal calcium and phosphate excretion through regulation of klotho expression

Rutkowski

Pastor

Sun

et al. 2017

Kidney International

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“…As discussed above, the level of circulating FGF21 is positively correlated with carotid intima-media thickness only in women but not in men [36]. Similarly, Lee et al observed that circulating FGF21 level is not correlated with bone mineral density (BMD) in man but it is positively correlated with BMD in healthy women even after adjustment for age and body composition [65]. It will be intriguing to know if the interaction between gender and FGF21 plays a role in its association with diabetes complications and the long-term outcome of FGF21 mimetic therapy.…”

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confidence: 84%

The role of fibroblast growth factor 21 in diabetes and its complications: A review from clinical perspective

Liu

Foo

Liu

et al. 2015

Diabetes Research and Clinical Practice

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“…With regards to chronic exercise, Bostrom et al ) also found no effect of long-term training on irisin level. Browning of WAT has not been observed after irisin/FNDC5 treatment in vitro (40,135) in humans. A study investigating the effect of FNDC5 treatment on human adipose cells found that UCP1 mRNA expression increased predominantly in classical brown adipocytes rather than white adipocytes (40).…”

Section: Assessment Of Bat and Browningmentioning

confidence: 96%

“…SNS activation is reflected by an increase in plasma and urinary noradrenaline levels in cold-exposed subjects (35,38,39,40,41). Denervation of sympathetic nerves abrogated the cold-induced changes in BAT activity in animals (42), providing strong evidence that SNS plays a pivotal role in mediating the stimulatory effect of cold on BAT.…”

Section: Assessment Of Bat and Browningmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Brown adipose tissue in humans: regulation and metabolic significance

Thuzar

2016

European Journal of Endocrinology

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The recent discovery that functional brown adipose tissue (BAT) persists in adult humans has enkindled a renaissance in metabolic research, with a view of harnessing its thermogenic capacity to combat obesity. This review focuses on the advances in the regulation and the metabolic significance of BAT in humans. BAT activity in humans is stimulated by cold exposure and by several factors such as diet and metabolic hormones. BAT function is regulated at two levels: an acute process involving the stimulation of the intrinsic thermogenic activity of brown adipocytes and a chronic process of growth involving the proliferation of pre-existing brown adipocytes or differentiation to brown adipocytes of adipocytes from specific white adipose tissue depots. BAT activity is reduced in the obese, and its stimulation by cold exposure increases insulin sensitivity and reduces body fat. These observations provide strong evidence that BAT plays a significant role in energy balance in humans and has the potential to be harnessed as a therapeutic target for the management of obesity.

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Fibroblast growth factor 21 (FGF21) and bone: is there a relationship in humans?

Cited by 50 publications

References 19 publications

Adiponectin alters renal calcium and phosphate excretion through regulation of klotho expression

Adiponectin alters renal calcium and phosphate excretion through regulation of klotho expression

The role of fibroblast growth factor 21 in diabetes and its complications: A review from clinical perspective

MECHANISMS IN ENDOCRINOLOGY: Brown adipose tissue in humans: regulation and metabolic significance

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