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Short-term alterations in carbohydrate energy intake in humans. Striking effects on hepatic glucose production, de novo lipogenesis, lipolysis, and whole-body fuel selection.

Short-term alterations in dietary carbohydrate (CHO) energy are known to alter whole-body fuel selection in humans, but the metabolic mechanisms remain unknown. We used stable isotope-mass spectrometric methods with indirect calorimetry in normal subjects to quantify the metabolic response to six dietary phases (5 d each), ranging from 50% surplus CHO (+50% CHO) to 50% deficient CHO (-50% CHO), and 50% surplus fat (+50% fat). Fasting hepatic glucose production (HGP) varied by > 40% from deficient to surplus CHO diets (1.78 +/- 0.08 vs 2.43 +/- 0.09 mg/kg per min, P < 0.01). Increased HGP on surplus CHO occurred despite significantly higher serum insulin concentrations. Lipolysis correlated inversely with CHO intake as did the proportion of whole-body lipolytic flux oxidized. Fractional de novo hepatic lipogenesis (DNL) increased more than 10-fold on surplus CHO and was unmeasurable on deficient CHO diets; thus, the preceding 5-d CHO intake could be inferred from DNL. Nevertheless, absolute hepatic DNL accounted for < 5g fatty acids synthesized per day even on +50% CHO. Whole-body CHO oxidation increased sixfold and fat oxidation decreased > 90% on surplus CHO diets. CHO oxidation was highly correlated with HGP (r2= 0.60). HGP could account for 85% of fasting CHO oxidation on +25% CHO and 67% on +50% CHO diets. Some oxidation of intracellular CHO stores was therefore also occurring. +50% fat diet had no effects on HGP, DNL, or fuel selection. We conclude that altered CHO intake alters HGP specifically and in a dose-dependent manner, that HGP may mediate the effects of CHO on whole-body fuel selection both by providing substrate and by altering serum insulin concentrations, that altered lipolysis and tissue oxidation efficiency contribute to changes in fat oxidation, and that surplus CHO is not substantially converted by the liver to fat as it spares fat oxidation, but that fractional DNL may nevertheless be a qualitative marker of recent CHO intake.

Body Weight↗

Limits to sustained energy intake. III. Effects of concurrent pregnancy and lactation in Mus musculus.

To determine whether mice were limited in their capacity to absorb energy during late lactation, we attempted to increase the energy burden experienced by a group of female mice during late lactation by mating them at the postpartum oestrus, hence combining the energy demands of pregnancy and lactation. These experimental mice were therefore concurrently pregnant and lactating in their first lactation, and were followed through a normal second lactation. In a control group, females also underwent two lactations but sequentially, with the second mating after the first litter had been weaned. Maternal mass and food intake were measured throughout the first lactation, second pregnancy and second lactation. Maternal resting metabolic rate (RMR) was measured prior to the first mating and then at the peak of both the first and second lactations. Litter size and litter mass were also measured throughout both lactations. In the first lactation, experimental mice had a lower mass-independent RMR (F1,88=5.15, P=0.026) and raised significantly heavier pups (t=2.77, d.f.=32, P=0.0093) than the control mice. Experimental mice delayed implantation at the start of the second pregnancy. The extent of the delay was positively related to litter size during the first lactation (F1,19=4.58, P=0.046) and negatively related to mean pup mass (F1,19=5.78, P=0.027) in the first lactation. In the second lactation, the experimental mice gave birth to more (t=2.75, d.f.=38, P=0.0092) and lighter (t=-5.01, d.f.=38, P<0.0001) pups than did the controls in their second lactation. Maternal asymptotic daily food intake of control mice in the second lactation was significantly higher (t=-4.39, d.f.=37, P=0.0001) than that of the experimental mice and higher than that of controls during their first lactation. Despite the added burden on the experimental females during their first lactation, there was no increase in their food intake, which suggested that they might be limited by their capacity to absorb energy. However, control females appeared to be capable of increasing their asymptotic food intake beyond the supposed limits estimated previously, suggesting that the previously established limit was not a fixed central limitation on food intake. As RMR increased in parallel with the increase in food intake during the second lactation of control mice, the sustained energy intake remained at around 7.0xRMR.

Animals↗

Energy intake and amyotrophic lateral sclerosis.

Roy Walford, a physician and scientist who pioneered research on the anti-aging effects of caloric restriction and subjected himself to a low-energy diet, recently died from amyotrophic lateral sclerosis (ALS). Information from his case, epidemiological findings, and recent controlled studies in mouse models of ALS suggest that low-energy diets might render motor neurons vulnerable to degeneration, whereas high-energy diets are ameliorative. This contrasts with the effects of low-energy diets on various neuronal populations in the brain that respond adaptively, activating pathways that promote plasticity and resistance to disease. One reason that motor neurons might be selectively vulnerable to low-energy diets is that they are unable to engage neuroprotective responses to energetic stress response involving the protein chaperones, such as, heat-shock protein-70.

Aging↗

Changing perspectives on aging and energy requirements: aging and energy intakes in humans, dogs and cats.

A series of cross-sectional and longitudinal studies conducted in humans has shown that aging is associated with a gradual decline in the maintenance energy requirement. Generally, this is equivalent to a total decrement of 20% of young adult maintenance energy requirements and is a result of a decrease in both physical activity and basal metabolic rate. Relatively few such studies have been conducted in dogs, but the results have been consistent. It appears that maintenance energy requirements decline by approximately 20%, and it is assumed that the causal factors are the same as those for humans. The situation appears to be somewhat different in cats, with evidence to date indicating that maintenance energy requirements remain constant throughout adult life. Why cats should be different from other species is not clear, but it is hypothesized that relative inactivity is typical of most cats' behavior, such that there is no obvious age-related change. In terms of feeding regimens for senior cats and dogs, it is appropriate to decrease energy provision for senior dogs by approximately 20%, whereas the energy provision for senior cats should not be decreased.

Adult↗

Reduced body weight, adipose tissue, and leptin levels despite increased energy intake in female mice lacking acylation-stimulating protein.

Acylation-stimulating protein (ASP) is a potent lipogenic protein produced by adipocytes. In vitro studies have shown that ASP increases triglyceride synthesis and glucose transport in both murine and human adipocytes. Our initial study indicated that complement C3-deficient (-/-) mice (and, therefore, ASP deficient) demonstrated altered dietary postprandial triglyceride clearance. In the present study we examined the phenotype of female mice longitudinally on different diets. Female C3(-/-) mice on both low (10% of energy) and high (40% of energy) fat diets displayed an average reduction in total body weight of 10.1+/-0.5% (P < 0.0003, by ANOVA) compared with the C3(+/+) littermates. Reductions in white adipose tissue mass accounted for most of this weight difference (59% reduction; P < 0.01 on low fat diet). Plasma leptin levels were significantly reduced in C3(-/-) mice on both high (P < 0.001) and low fat diets (P < 0.01). This reduction was significant even after adjusting for the reduced body weight and body fat (P < 0.001). Leptin reductions in the C3(-/-) were greater on the high fat diet and were associated with increased food intake (18+/-2% increase; P < 0.001). Furthermore, there was a decrease in basal glucose levels and basal insulin levels [12.8% decrease in glucose at 14 weeks (HF; P < 0.05) and 41% decrease in insulin at 26 weeks (HF; P < 0.05)]. These in vivo experiments demonstrate that female mice lacking ASP have marked alterations of body weight, adiposity, plasma leptin, and plasma insulin levels. Decreased adiposity and leptin levels occurred in the ASP-deficient animals despite increased energy intake, suggesting that energy expenditure was elevated in these animals. Thus, ASP appears to have an important role in the regulation of energy balance in mice.

Adipose Tissue↗

Nutritional status of Danish rheumatoid arthritis patients and effects of a diet adjusted in energy intake, fish-meal, and antioxidants.

This study deals with the nutritional status of Danish RA patients and address the question of whether or not RA can be directly influenced by dietary manipulation. In a prospective, single-blinded study of 6 months duration, 109 patients with active RA were randomly assigned to either treatment with or without a specialized diet. The energy consumption was adjusted to normal standards of body weights and the intake of fish meals and antioxidants were increased. A daily food diary was completed by the patients, and the total intake of 47 different food-elements was calculated. Nutritional status together with disease activity parameters were recorded. At baseline, the Danish RA-patients had neglected food habits with a significant reduction in intake of total energy, of D-vitamin and of E-vitamin. A very low intake of n-3 fatty acids was also found. During the study, 28 of the 109 patients dropped out, introducing a confounding effect on the overall result. In the remaining 81, those following the diet demonstrated a significant improvement in the duration of morning stiffness, number of swollen joints, pain status, and reduced cost of medicine, while doctors global assessment, laboratory data, X-ray, and daily activities were unaltered. In conclusion, dietary analysis and appropriate, corrective advice should be offered to Danish RA patients.

Arthritis, Rheumatoid↗

Is a low fat diet the optimal way to cut energy intake over the long-term in overweight people?

Successful weight loss depends on maintaining a sustained negative energy balance. This can be achieved on diets with a normal (40% energy) fat content as well as on low fat diets. Using a 'modified fat' (MF) diet enriched with monounsaturated fat (MUFA), body weight may be lost either by calorie counting, or by allowing ad libitum food intake with careful food selection. In the latter approach high energy, high MUFA foods (predominantly olive oil, but also may include nuts and avocado) should contribute no more than 20% total energy to the diet, and other foods should be selected to minimise meal energy density. This can be achieved simply by the consumption of a wide variety of vegetables and whole grain cereal foods. It is also important to restrict foods high in saturated fat and to encourage regular exercise. Such a 'modified fat' low energy diet designed for weight loss should also contribute numerous health benefits in relation to improved metabolic control in Type 2 diabetes and reduced cardiovascular disease risk (as the diet is not only rich in MUFA but also in a range of dietary antioxidants and other bio-active phytochemicals).

Diet, Fat-Restricted↗