The role of leptin in regulating bone metabolism

Upadhyay, Jagriti; Farr, Olivia M.; Mantzoros, Christos S.

doi:10.1016/j.metabol.2014.10.021

Cited by 201 publications

(147 citation statements)

References 111 publications

Supporting

Mentioning

134

Contrasting

Unclassified

Order By: Relevance

“…Leptin signaling has been suggested to affect bone metabolism directly through effects on osteoblasts and indirectly through altered activity of the (sympathetic) nervous system, GH, IGF1, parathyroid and thyroid hormones, cortisol and estrogen [12]. The finding that obese subjects with a mutation in MC4R , which acts downstream of the LEPR, also have a high BMD [37] suggests that leptin may act on proopiomelanocortin-producing neurons and then through the melanocortin 4 receptor on paraventricular neurons to influence bone metabolism.…”

Section: Discussionmentioning

confidence: 99%

“…(clinical features of) altered immune function/T-cell numbers [3,4,7,10], hypogonadotropic hypogonadism [3,6,8], reduced growth hormone (GH) secretion [2,8], hypothalamic hypothyroidism [2,8], and reduced adult height [3]. No data are available on bone health in these patients, although LEPR is known to be involved in bone metabolism [11,12]. …”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Hannema¹,

Wit²,

Houdijk³

et al. 2016

Horm Res Paediatr

View full text Add to dashboard Cite

Background: Recessive mutations in the leptin receptor (LEPR) are a rare cause of hyperphagia and severe early-onset obesity. To date, the phenotype has only been described in 25 obese children, some of whom also had altered immune function, hypogonadotropic hypogonadism, reduced growth hormone secretion, hypothalamic hypothyroidism or reduced adult height. We provide a detailed description of the phenotype of 2 affected girls to add to this knowledge. Methods: Whole-exome sequencing and targeted sequencing were used to detect the LEPR mutations. RNA analysis was performed to assess the effect of splice-site mutations. Results: In 2 unrelated girls with severe obesity, three novel LEPR mutations were detected. Longitudinal growth data show normal childhood growth, and in the older girl, a normal adult height despite hypogonadotropic hypogonadism and the lack of an obvious pubertal growth spurt. Bone age is remarkably advanced in the younger (prepubertal) girl, and bone mineral density (BMD) is high in both girls, which might be directly or indirectly related to leptin resistance. Conclusion: The spectrum of clinical features of LEPR deficiency may be expanded with increased BMD. Future observations in LEPR-deficient subjects should help further unravel the role of leptin in human bone biology.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Hannema¹,

Wit²,

Houdijk³

et al. 2016

Horm Res Paediatr

View full text Add to dashboard Cite

show abstract

“…Additionally, leptin also appears to activate pro-inflammatory pathways in osteoblasts (Upadhyay et al 2015), contributing even more toward bone deterioration. Conversely, decreased serum leptin is found in frail elderly and in cachexia (Hubbard et al 2008).…”

Section: Muscle As Endocrine Organmentioning

confidence: 99%

Aging human body: changes in bone, muscle and body fat with consequent changes in nutrient intake

Jafarinasabian

Inglis

Reilly

et al. 2017

Journal of Endocrinology

192

137

View full text Add to dashboard Cite

Aging affects almost all physiological processes, but changes in body composition and body phenotype are most observable. In this review, we focus on these changes, including loss of bone and muscle and increase in body fat or redistribution of the latter, possibly leading to osteosarcopenic obesity syndrome. We also address low-grade chronic inflammation, prevalent in aging adults and a cause of many disorders including those associated with body composition. Changes in dietary intake and nutritional requirements of older individuals, that all may lead to some disturbances on tissue and organ levels, are discussed as well. Finally, we discuss the hormonal changes in the aging body, considering each of the tissues, bone, muscle and fat as separate endocrine organs, but yet in the continuous interface and communication with each other. Although there are still many unanswered questions in this field, this review will enable the readers to better understand the aging human body and measures needing to be implemented toward reducing impaired health and disability in older individuals.

show abstract

“…Alterations in peripheral [13] and/or central leptin signalling [14] may be factors influencing DIO-induced bone loss, given that rodents fed high-fat [15] or high-fructose diets [16] exhibit chronically elevated circulating leptin and that leptin is negatively associated with BMD in mice with DIO resulting from high-fat feeding. [10] In this regard, leptin is an adipocyte-derived hormone that increases proportionally with adiposity and which influences bone accrual via central [14] and peripheral manners.…”

Section: Introductionmentioning

confidence: 99%

Fructose consumption does not worsen bone deficits resulting from high-fat feeding in young male rats

Yarrow

Toklu

Balaez

et al. 2016

Bone

View full text Add to dashboard Cite

Dietary-induced obesity (DIO) resulting from high-fat (HF) or high-sugar diets produces a host of deleterious metabolic consequences including adverse bone development. We compared the effects of feeding standard rodent chow (Control), a 30% moderately HF (starch-based/sugar-free) diet, or a combined 30%/40% HF/high-fructose (HF/F) diet for 12 weeks on cancellous/cortical bone development in male Sprague-Dawley rats aged 8 weeks. Both HF feeding regimens reduced the lean/fat mass ratio, elevated circulating leptin, and reduced serum total antioxidant capacity (tAOC) when compared with Controls. Distal femur cancellous bone mineral density (BMD) was 23–34% lower in both HF groups (p<0.001) and was characterized by lower cancellous bone volume (BV/TV, p<0.01), lower trabecular number (Tb.N, p<0.001), and increased trabecular separation versus Controls (p<0.001). Cancellous BMD, BV/TV, and Tb.N were negatively associated with leptin and positively associated with tAOC at the distal femur. Similar cancellous bone deficits were observed at the proximal tibia, along with increased bone marrow adipocyte density (p<0.05), which was negatively associated with BV/TV and Tb.N. HF/F animals also exhibited lower osteoblast surface and reduced circulating osteocalcin (p<0.05). Cortical thickness (p<0.01) and tissue mineral density (p<0.05) were higher in both HF-fed groups versus Controls, while whole bone biomechanical characteristics were not different among groups. These results demonstrate that “westernized” HF diets worsen cancellous, but not cortical, bone parameters in skeletally-immature male rats and that fructose incorporation into HF diets does not exacerbate bone loss. In addition, they suggest that leptin and/or oxidative stress may influence DIO-induced alterations in adolescent bone development.

show abstract

The role of leptin in regulating bone metabolism

Cited by 201 publications

References 111 publications

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Novel Leptin Receptor Mutations Identified in Two Girls with Severe Obesity Are Associated with Increased Bone Mineral Density

Aging human body: changes in bone, muscle and body fat with consequent changes in nutrient intake

Fructose consumption does not worsen bone deficits resulting from high-fat feeding in young male rats

Contact Info

Product

Resources

About