Free fatty acid and glucose metabolism in human aging: evidence for operation of the Randle cycle

Abstract

We assessed insulin effects on plasma free fatty acid (FFA) and glucose metabolism in seven elderly (71 +/- 2 yr) and in seven younger (21 +/- 1 yr) subjects matched for body weight and body mass index but not for percent body fat (32.4 +/- 3.8% in elderly vs. 20.4 +/- 3.5% in young, P < 0.05), by performing sequential euglycemic clamps at five insulin doses (0.6, 1.5, 3, 6, and 15 pmol.min-1.kg-1) in combination with indirect calorimetry and [1-14C]palmitate plus [3-3H]glucose infusion. At baseline, plasma FFA concentration, turnover infusion. At baseline, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were all increased in the elderly (897 +/- 107 vs. 412 +/- 50 mumol/l and 11.2 +/- 1.4 vs. 5.14 +/- 0.86, 3.45 +/- 0.65 vs. 1.37 +/- 0.25, and 4.63 +/- 0.72 vs. 3.01 +/- 0.33 mumol.min-1.kg-1 lean body mass, P < 0.05 for all comparisons), whereas glucose turnover was similar as a result of decreased glucose oxidation (8.2 +/- 1.4 vs. 13 +/- 1.9 mumol.min-1.kg-1 lean body mass, P < 0.05) and increased glucose storage (6.6 +/- 1.4 vs. 1.7 +/- 1.3 mmol.min-1.kg-1 lean body mass, P < 0.05). At all insulin infusions, plasma FFA concentration, turnover and oxidation, and total lipid oxidation were higher in the elderly than in the younger group (P < 0.05). However, if normalized per fat mass, all FFA and lipid metabolic fluxes, both in the postabsorptive state and during hyperinsulinemia, were comparable in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

“…In another study in Fischer-344 rats, total plasma PUFA percent composition increased with age (Engler et al 1998). In humans, total unesterified fatty acid concentrations increased with age (Bonadonna et al 1994), as did EPA and DHA concentrations in plasma total lipids (Balkan et al 2002;Fortier et al 2010). The inconsistency in study outcomes may relate to differences in DHA synthesis capacity between rodents and humans (Wang et al 2006), diet, or the fact that most studies measured n-3 PUFA concentrations in plasma total lipid instead of esterified and unesterified fractions (Engler et al 1998;Fortier et al 2010).…”

Age is an Important Risk Factor for Type 2 Diabetes Mellitus and Cardiovascular Diseases

“…Effects of insulin on plasma FFA was different between in the elderly compared with in younger subjects. Insulin infusions showed that plasma FFA, turnover and oxidation, and total lipid oxidation were higher significantly in the elderly than in the younger group (Bonadonna et al, 1994). Aging is also associated with decreased sensitivity to antilipolysis effects of insulin (Toth and Tchernof, 2000).…”

Lipid metabolism in the elderly

“…In fact, free fatty acids are released in excess of energy needs in older individuals when compared to younger controls. For example, under resting conditions, free fatty acid rate of appearance is greater in older men and women despite reduced resting energy expenditure (Bonadonna et al, 1994;Toth et al, 1996). Moreover, during exercise of the same caloric expenditure, the rate of appearance of free fatty acid was greater in older compared to younger individuals (Sial et al, 1996).…”

“…Aging is associated with reduced sensitivity to the anti-lipolytic effect of insulin in isolated adipocytes (Bolinder et al, 1983). Moreover, in vivo studies show that both the time course for the suppression of plasma free fatty acids (Coon et al, 1992) and the dose±response suppression of free fatty acid appearance by insulin (Bonadonna et al, 1994) are diminished with age. Thus, resistance to the anti-lipolytic effect of insulin may account for the excess release of free fatty acids in older individuals.…”

“…It should be pointed out, however, that increased free fatty acid release in older individuals may simply result from increased adipose tissue mass. Indeed, the rate of appearance of free fatty acids are either similar between older and younger individuals or greater in younger individuals when expressed per unit adipose tissue mass (Bonadonna et al 1994;Klein et al, 1986). Whatever the mechanism, reduced free fatty acid availability secondary to diminished release of free fatty acids from adipose tissue does not appear to be a factor contributing to reduced fat oxidation with age.…”