Altered structure and function of adipose tissue in long-lived mice with growth hormone-related mutations

Abstract

A major focus of biogerontology is elucidating the role(s) of the endocrine system in aging and the accumulation of age-related diseases. Endocrine control of mammalian longevity was first reported in Ames dwarf (Prop1 df ) mice, which are long-lived due to a recessive Prop1 loss-of-function mutation resulting in deficiency of growth hormone (GH), thyroid-stimulating hormone, and prolactin. Following this report, several other GH-related mutants with altered longevity have been described including long-lived Snell dwarf and growth hormone receptor knockout mice, and shortlived GH overexpressing transgenic mice. One of the emerging areas of interest in these mutant mice is the role of adipose tissue in their altered healthspan and lifespan. Here, we provide an overview of the alterations in body composition of GH-related mutants, as well as the altered thermogenic potential of their brown adipose tissue and the altered cellular senescence and adipokine production of their white adipose tissue.

Increased environmental temperature normalizes energy metabolism outputs between normal and Ames dwarf mice

“…Moreover, dwarf mice had an increase in relative subcutaneous adipose tissue weight compared to their normal littermates, whereas normal mice had an increase in relative epididymal adipose tissue weight compared to dwarf mice. While the differences in deposition, structure, and function of adipose tissue in GH mutant mice are beyond the scope of this article, interested readers are directed to several relevant review articles [ 22 – 24 ]. Ames dwarfs had an increase in the relative weight of their BAT as previously reported [ 13 ].…”

Biomaterials to Mimic and Heal Connective Tissues

“…[50] Since growth hormone is lipolytic, growth hormone deficient and resistant mice increase in body fat with aging. [51] Aging also causes adipose progenitor cell dysfunction [52] senescent cell accumulation, [53] ectopic lipid deposition, [54,55] and adipose tissue miRNA processing. [56] Indeed, several interventions aimed to reduce aged-induced changes in WAT include caloric restriction, growth hormone reduction, and estradiol.…”

Mice with gene alterations in the GH and IGF family

“…These dwarf mice are protected from HFD-induced insulin resistance unlike agematched WT mice [88]. Additional distinct physiological characteristics of Ames mice include significantly higher brown AT [89], lower resting core body temperature [90], and a reduced senescent cell burden in white AT [91]. Similar to Snell mice, Ames mice are also markedly resistant to standard oxidative stress inducers like paraquat and diaquat, even at older ages [92].…”