Effects of Moderate Chronic Food Restriction on the Development of Postprandial Dyslipidemia with Ageing

Abstract

Ageing is a major risk factor for the development of metabolic disorders linked to dyslipidemia, usually accompanied by increased adiposity. The goal of this work was to investigate whether avoiding an excessive increase in adiposity with ageing, via moderate chronic food restriction (FR), ameliorates postprandial dyslipidemia in a rat model of metabolic syndrome associated with ageing. Accordingly, we performed an oral lipid loading test (OLLT) in mature middle-aged (7 months) and middle-old-aged (24 months) Wistar rats fed ad libitum (AL) or under moderate FR for 3 months. Briefly, overnight fasted rats were orally administered a bolus of extra-virgin olive oil (1 mL/Kg of body weight) and blood samples were taken from the tail vein before fat load (t = 0) and 30, 60, 90, 120, 180, and 240 min after fat administration. Changes in serum lipids, glucose, insulin, and glucagon levels were measured at different time-points. Expression of liver and adipose tissue metabolic genes were also determined before (t = 0) and after the fat load (t = 240 min). Postprandial dyslipidemia progressively increased with ageing and this could be associated with hepatic ChREBP activity. Interestingly, moderate chronic FR reduced adiposity and avoided excessive postprandial hypertriglyceridemia in 7- and 24-month-old Wistar rats, strengthening the association between postprandial triglyceride levels and adiposity. The 24-month-old rats needed more insulin to maintain postprandial normoglycemia; nevertheless, hyperglycemia occurred at 240 min after fat administration. FR did not alter the fasted serum glucose levels but it markedly decreased glucagon excursion during the OLLT and the postprandial rise of glycemia in the 24-month-old rats, and FGF21 in the 7-month-old Wistar rats. Hence, our results pointed to an important role of FR in postprandial energy metabolism and insulin resistance in ageing. Lastly, our data support the idea that the vWAT might function as an ectopic site for fat deposition in 7-month-old and in 24-month-old Wistar rats that could increase their browning capacity in response to an acute fat load.

Low‐Intensity Exercise Routine for a Long Period of Time Prevents Osteosarcopenic Obesity in Sedentary Old Female Rats, by Decreasing Inflammation and Oxidative Stress and Increasing GDF‐11

“…Age-related fat gain is known to correlate with muscle and bone deterioration during OSO [35,46]. Moreover, it has been observed that body fat increases in Wistar rats throughout life, which has been related to a decrease in muscle mass, BMC, and life expectancy [57][58][59][60]. As mentioned before, one of the main benefits observed in the LIERLT routine was that reducing body fat increased the survival of Wistar female rats by 66%.…”

Aging Induces Hepatic Oxidative Stress and Nuclear Proteomic Remodeling in Liver from Wistar Rats

“…On the contrary, insulinemia was increased in old rats following 36 h of fasting, according to their insulin-resistant state [15][16][17][18]. As previously reported [15][16][17][18], no differences were observed between 3-and 24month-old Wistar rats with respect to serum glucose and NEFA concentration after 16 or 36 h of fasting. NEFA concentrations decreased to a similar extent in both groups of rats after 36 h of fasting.…”

“…Thus, the 24-month-old rats used in the present study were middle-old age animals. These old rats were not at high risk of mortality and did not present apparent signs of frailty [15][16][17]36], although they showed higher intracellular accumulation of lipofuscin, compared to 3-month-old Wistar rats [17], a marker of cellular senescence.…”

“…The old Wistar rat is a physiological model of aging with metabolic disorders like those observed in the human MS, including increases in visceral fat, dyslipidemia, and insulin resistance. In addition, and closely related to dyslipidemia and insulin resistance, the aged Wistar rat manifests adipose tissue inflammation and liver steatosis and fibrosis [15][16][17][18]. Most of our knowledge about the molecular changes that occur in the liver of Wistar rats with aging comes from studies of gene expression and protein distribution patterns [16].…”

“…Most of our knowledge about the molecular changes that occur in the liver of Wistar rats with aging comes from studies of gene expression and protein distribution patterns [16]. In this regard, we published that aging causes a significant increase in the mRNA abundance of lipogenic transcription factors and enzymes, such as carbohydrateresponsive element-binding protein (ChREBP), diacylglycerol acyltransferases 1 and 2 (DGAT1/2), and microsomal triglyceride transfer protein (MTTP), whereas the mRNA levels of the forkhead transcription factor Foxa2 and the most important enzyme associated with mitochondrial fatty acid oxidation carnitine-palmitoyl transferase-1 (CPT-1a) were markedly decreased in the liver of old Wistar rats [16,17]. Contrary to what was observed in young rats, lipogenic ChREBP was enriched in the nuclear fraction of liver homogenate from old rats under 36 h fasting, whereas oxidative Foxo1 and Foxa2 were enriched in the cytoplasmic fraction [16].…”