Visceral adipose tissue modulates mammalian longevity

Abstract

SummaryCaloric restriction (CR) can delay many age-related diseases and extend lifespan, while an increase in adiposity is associated with enhanced disease risk and accelerated aging. Among the various fat depots, the accrual of visceral fat (VF) is a common feature of aging, and has been shown to be the most detrimental on metabolic syndrome of aging in humans. We have previously demonstrated that surgical removal of VF in rats improves insulin action; thus, we set out to determine if VF removal affects longevity. We prospectively studied lifespan in three groups of rats: ad libitum -fed (AL-fed), CR (Fed 60% of AL) and a group of AL-fed rats with selective removal of VF at 5 months of age (VF-removed rats). We demonstrate that compared to AL-fed rats, VF-removed rats had a significant increase in mean ( p < < < < 0.001) and maximum lifespan ( p < < < < 0.04) and significant reduction in the incidence of severe renal disease ( p < < < < 0.01). CR rats demonstrated the greatest mean and maximum lifespan ( p < < < < 0.001) and the lowest rate of death as compared to AL-fed rats (0.13). Taken together, these observations provide the most direct evidence to date that a reduction in fat mass, specifically VF, may be one of the possible underlying mechanisms of the antiaging effect of CR. Key words: aging; lifespan; obesity; caloric restriction; visceral fat removal.Caloric restriction (CR) extends lifespan in a variety of species (Weindruch, 1996). In contrast, obesity is a major risk factor for several age-related diseases and has been estimated to markedly lessen life expectancy (Fontaine et al ., 2003). Visceral fat (VF) accretion occurs in obesity and with aging, and a reduction in VF is a common phenotypic change in calorie-restricted mammals (Barzilai & Gupta, 1999). VF has been shown to be the single most important determinant of metabolic syndrome (Carr et al ., 2004), and its removal in rats results in improved insulin action and delays the onset of diabetes Gabriely et al ., 2002). Given the hazards associated with abdominal obesity, it seems plausible that the beneficial effects of CR on longevity may be due at least in part to an attenuation of VF (Barzilai & Gupta, 1999). Here we study the effects of VF removal on the lifespan of rats.We prospectively studied lifespan in three groups of rats: ad libitum -fed (AL-fed), CR (Fed 60% of AL) and a group of AL-fed rats with selective removal of VF at 5 months of age (VF-removed rats). At 20 months of age, a subgroup of animals ( n = 8 per group) were killed to assess body fat distribution. There was no significant difference in body weights among all three groups at the beginning of the study (8 weeks of age) nor were body weights significantly different between AL-fed and VF-removed rats throughout their lifespan (Fig. 1A). However, maximal body weight was achieved at an earlier age in AL-fed rats (69 ± 3 weeks; mean ± SD) than in VF-removed rats (79 ± 3 weeks; p < 0.001), indicating a delay in the age-related weight decline in VF-removed animals. Although V...

Ectopic fat deposition contributes to age-associated pathology in Caenorhabditis elegans

“…Consistent with the previous reported effects of caloric restriction on ectopic fat deposition (49,50), eat-2(ad465) animals display decreased rate of ectopic lipid storage in pharyngeal muscles compared with their wild-type counterparts during aging (Fig. 4A, B).…”

“…Affected individuals display greater risk for developing type 2 diabetes, increased inflammation, cognitive impairment, and accelerated functional decline (78,79). Caloric restriction delays or prevents several potentially harmful age-associated phenotypes, which are known to be involved in metabolic syndrome progression (49,50). To this direction, we observed decreased levels of ectopic fat deposition in caloric-restricted eat-2(ad465) mutants compared with wild-type nematodes during aging.…”

“…This dietary manipulation is referred as caloric restriction. In mammals, nutrient deprivation results in the delay of numerous detrimental age-associated hallmarks, such as increased adiposity, abdominal fat, and impaired hepatic and peripheral insulin action (49,50). Although caloric restriction effect on primate life span remains ambiguous, its beneficial impact on preventing a variety of age-related pathologies is generally accepted (51)(52)(53).…”

Methionine restriction improves renal insulin signalling in aged kidneys

“…Surgical removal of visceral fat or reduction in adiposity by caloric restriction (CR), are effective strategies in rodents for increasing lifespan and enhancing insulin sensitivity (2)(3)(4). Reducing dietary levels of the essential amino acid methionine also extends lifespan (5,6).…”

Obesity and aging have divergent genomic fingerprints

“…Conversely, recent studies in mice and in humans have indicated that WAT accumulation could negatively influence longevity, 1,2 whereas a surgical or genetically engineered reduction in WAT mass in rodents could prolong lifespan. [3][4][5][6] This has led various investigators to the postulate that obesity could be considered as a condition of premature metabolic aging. We explored this hypothesis by profiling obesity and agemediated changes in gene expression in visceral WAT using whole-genome microarray technology in mice.…”