Circadian Feeding Drive of Metabolic Activity in Adipose Tissue and not Hyperphagia Triggers Overweight in Mice: Is There a Role of the Pentose-Phosphate Pathway?

Abstract

High-fat (HF) diets trigger an increase in adipose tissue and body weight (BW) and disordered eating behavior. Our study deals with the hypothesis that circadian distribution of energy intake is more relevant for BW dynamics than diet composition. Four-week-old mice were exposed for 8 wk to a HF diet and compared with animals receiving control chow. HF mice progressively increased BW, decreased the amount of nocturnal (1800-0900 h) calories (energy or food intake) (30%) and increased diurnal (0900-1800 h) caloric intake (energy or food intake), although total daily intake was identical between groups. Animals were killed at 3-h intervals and plasma insulin, leptin, corticosterone, glucose, and fatty acid levels quantified. Adipose tissue was weighed, and enzymatic activities integral to the pentose phosphate pathway (PPP) assayed in lumbar adipose tissue. Phosphorylated AMP-dependent protein kinase and fatty acid synthase were quantified by Western blotting. In HF mice, there was a shift in the circadian oscillations of plasma parameters together with an inhibition of PPP activity and a decrease in phosphorylated AMP-dependent protein kinase and fatty acid synthase. In a second experiment, HF mice were forced to adhere to a circadian pattern of food intake similar to that in control animals. In this case, BW, adipose tissue, morning plasma parameters and PPP activity appeared to be normal. These data indicate that disordered feeding behavior can trigger BW gain independently of food composition and daily energy intake. Because PPP is the main source of reduced nicotinamide adenine dinucleotide phosphate, we suggest that PPP inhibition might be an early marker of adipose dysfunction in diet-induced obesity.

Impact of fasting on the rhythmic expression of myogenic and metabolic factors in skeletal muscle of adult mice

“…Instead, we weighed the stomach content of each freely fed mouse following death and these results accord with the previously described feeding pattern of adult male C57Bl/6J mice (46,51). Adult C57Bl/6J mice consume food throughout 24 h with a reduced food intake during light hours and intense feeding during dark hours: the highest food intake occurs during the first 6 h of the dark phase (51). This is consistent with the present results of decreased Table 1.…”

Decreased rates of operant food self-administration are associated with reward deficits in high-fat feeding mice

“…In contrast, the effect was only observed after 8-week treatment during the light phase. At this point, it has to be stated that HFD triggers relevant changes in distribution of meals characterized by an increase in food intake during the light period and slight hypophagia during the night [37], thus suggesting that demotivation for food rather affects nocturnal feeding. Our current data give support to the inhibitory effect of HFD [26] as they show that this kind of diets reduces motivation for food also during the light period and point to the inhibition of food reward as a main trigger of changes in feeding behavior leading to obesity.…”

“…The connection between reward deficits and obesity exceeds the goal of the current study, but we have already proposed that circadian desynchronization of meals triggered by HFD may be a pivotal trigger event. Indeed, we have observed that forced synchronization of food intake prevents obesity and allows recover reward performance [26,37,48]. Otherwise, mismatch between feeding and light/dark cycle has been shown to disrupt energy metabolism in skeletal muscle and has significant consequences for whole-body energy homeostasis [49].…”

Involvement of the dorsomedial prefrontal cortex in high-fat food conditioning in adolescent mice

“…We have previously shown that HFD-induced obese (DIO) mice initially display hyperphagia that is followed by sustained normoor even hypophagia [4]. Moreover, during this second period, circadian desynchronization of feeding has been shown to precede metabolic alterations typical of obesity [4][5][6] and DIO mice exhibit a lack of motivation for natural and non-natural reinforcers [7].…”

“…Moreover, during this second period, circadian desynchronization of feeding has been shown to precede metabolic alterations typical of obesity [4][5][6] and DIO mice exhibit a lack of motivation for natural and non-natural reinforcers [7]. Because naive mice, metabolically unaltered, exposed to HFD rapidly display hyperphagia, we aimed at further characterizing the rewarding component of such behavior as well as neuronal targets sensitive to HFD.…”