Severe Caloric Restriction Research Articles

Role for Sit4p‐dependent mitochondrial dysfunction in mediating the shortened chronological lifespan and oxidative stress sensitivity of Isc1p‐deficient cells

Saccharomyces cerevisiae cells lacking Isc1p, an orthologue of mammalian neutral sphingomyelinase 2, display a shortened lifespan and an increased sensitivity to oxidative stress. A lipidomic analysis revealed specific changes in sphingolipids that accompanied the premature ageing of Isc1p-deficient cells under severe calorie restriction conditions, including a decrease of dihydrosphingosine levels and an increase of dihydro-C(26) -ceramide and phyto-C(26) -ceramide levels, the latter raising the possibility of activation of ceramide-dependent protein phosphatases. Consequently, deletion of the SIT4 gene, which encodes for the catalytic subunit of type 2A ceramide-activated protein phosphatase in yeast, abolished the premature ageing and hydrogen peroxide sensitivity of isc1Δ cells. SIT4 deletion also abolished the respiratory defects and catalase A deficiency exhibited by isc1Δ mutants. These results are consistent with catabolic derepression associated with the loss of Sit4p. The overall results show that Isc1p is an upstream regulator of Sit4p and implicate Sit4p activation in mitochondrial dysfunction leading to the shortened chronological lifespan and oxidative stress sensitivity of isc1Δ mutants.

A Recent Update on the Role of Ghrelin in Glucose Homeostasis

Recent evidence highlights an important role of ghrelin in glucose homeostasis. In this review we provide a detailed summary of recent advances in this field. We describe the effects of ghrelin on all aspects of glucose homeostasis including glucose-stimulated insulin secretion, hepatic glucose production and insulin stimulated glucose disposal in the peripheral tissues. The existing evidence suggests ghrelin primarily inhibits insulin release from the pancreas and we highlight an important mechanism involving AMPK-UCP2 ATP-stimulated potassium channels and intracellular calcium regulation. Ghrelin increases hepatic glucose production and prevents glucose disposal in muscle and adipose tissues, which collectively leads to hyperglycemia and impaired glucose tolerance. We discuss the important role ghrelin plays in glucose homeostasis during different metabolic states. During severe calorie restriction, ghrelin increases blood glucose concentrations in order to maintain glucose homeostasis. In diet-induced obesity, ghrelin exacerbates hyperglycemia and promotes a diabetic phenotype.

Blood glucose regulation during fasting in rats under food restriction since birth

The effect of severe food restriction since birth o n regulation of fasting glycemia in male Wistar rat s was investigated. The control group (CG) had free suppl y of chow, while the restriction group (RG) receive d 50% of the amount ingested by the CG. The experiments were don e in adult (60 days) overnight fasted rats in which glycemia, liver free glucose levels and hepatic glycogen conc entration were measured. In part of the experiments in situ liver perfusion was done. The results showed that livers from the RG had higher glycogenolysis rates but low er gluconeogenesis rates from L-alanine (10 mM). Since RG showed maintained glycemia during fasting, it c ould be concluded that livers from RG produced glucose pref erentially from glycogenolysis in detriment of gluc oneogenesis. These findings demonstrated that in spite of severe caloric restriction, the metabolic adaptations of the liver did exist to assure the maintenance of blood glucose fo r brain supply during fasting.

Ghrelin and growth hormone: Story in reverse

The current epidemic of obesity and diabetes in the face of a surfeit of calories contrasts the natural selection to survive famine that confronted our ancestors. The report in PNAS by Zhao et al. (1) shows that ghrelin is an important hormone in this process. By studying mice under severe caloric restriction, they show that knockout (KO) of the enzyme ghrelin O-acyltransferase (GOAT), necessary to convert ghrelin to its active form, manifests the first clear phenotype seen in KO of ghrelin activity; ghrelin is necessary for triggering the growth-hormone (GH) response to nutritional deprivation that prevents hypoglycemia and death.

Ghrelin O -acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice

Ghrelin O-acyltransferase (GOAT) attaches octanoate to proghrelin, which is processed to ghrelin, an octanoylated peptide hormone that stimulates release of growth hormone (GH) from pituitary cells. Elimination of the gene encoding ghrelin or its receptor produces only mild phenotypes in mice. Thus, the essential function of ghrelin is obscure. Here, we eliminate the Goat gene in mice, thereby eliminating all octanoylated ghrelin from blood. On normal or high fat diets, Goat(-/-) mice grew and maintained the same weights as wild-type (WT) littermates. When subjected to 60% calorie restriction, WT and Goat(-/-) mice both lost 30% of body weight and 75% of body fat within 4 days. In both lines, fasting blood glucose initially declined equally. After 4 days, glucose stabilized in WT mice at 58-76 mg/dL. In Goat(-/-) mice, glucose continued to decline, reaching 12-36 mg/dL on day 7. At this point, WT mice showed normal physical activity, whereas Goat(-/-) mice were moribund. GH rose progressively in calorie-restricted WT mice and less in Goat(-/-) mice. Infusion of either ghrelin or GH normalized blood glucose in Goat(-/-) mice and prevented death. Thus, an essential function of ghrelin in mice is elevation of GH levels during severe calorie restriction, thereby preserving blood glucose and preventing death.

Variable Effects of Caloric Restriction on Metabolic and Breathing Regulation Between Two Inbred Mouse Strains

The World Health Organization reports that ~800 million people worldwide are undernourished, corresponding to a daily mortality rate of 25,000 people. While altered metabolic and breathing characteristics occur with severe caloric restriction (CR), the mechanisms are unclear. We hypothesize that a robust genetic difference between C3H/HeJ (C3) and C57BL/6 (B6) mice lead to variation in metabolic and breathing regulation with CR. C3 and B6 mice (n = 8 per strain) were fed a diet equal to 33% of the daily food intake for 21 days. Using plethysmography, breathing characteristics were measured weekly on room air, and following acute hypercapnic (5% CO2) and hypoxic (10% O2) challenges. While the decline in body weight through 21 days of CR was similar in C3 vs. B6 strains (~40%), reductions in body temperature (10.0±1.8 vs. 2.8±1.0°C) and O2 consumption (1.36±0.32 vs. ‐0.04±0.16 ml/hr/g) were significantly (P < 0.01) lower in C3 relative to B6 mice. Minute ventilation (VE) on room air remained unchanged with CR in both strains, but hypercapnic and hypoxic VE were depressed incrementally though 14 days. By day 21 of CR, hypercapnic and hypoxic VE recovered in B6 but not in C3 mice. In conclusion, genetic factors determine variation in metabolic and breathing regulation during CR, allowing B6 mice to maintain indices of homeostasis closer to control values than C3 mice.

Aging, IGF‐1, and diet

Fontana et al. (2008) recently reported in Aging Cell their interesting findings, based on studies of 46 subjects, of the impact of chronic severe caloric restriction on insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) levels. They concluded that protein intake may be a more important determinant of the circulating levels than energy restriction, and speculated that this may have implications with respect to longevity. We previously reported (Holmes et al. , 2002; Giovannucci et al. , 2003) studies of 1037 women and 753 men that explored dietary determinants of IGF-1 and IGFBP-3 levels in a crosssection of subjects on typical North American diets. We observed, in females, a positive association between protein intake with circulating IGF-1 concentration (174, 188, 201, 192, and 196 ng mL –1 across quintiles of protein intake; p = 0.002), which was stronger than the relationship between energy intake and IGF-1 concentration. Similar findings were seen in men, where the relationship of energy intake to IGF-1 levels was seen only in men with body mass index < 25 kg m –2 . Thus, the intervention study involving a small number of subjects by Fontana et al. yielded data consistent with the larger observational studies we previously reported. Caution is required in extrapolating data concerning dietaryinduced changes in IGF-1 levels to changes in health outcomes, such as longevity or cancer risk. While there is clear evidence that reduced IGF signalling is associated with increased longevity in model organisms, there is evidence that lower IGF-1 levels are associated with increased cardiovascular disease in humans (Brugts et al. , 2008). In addition, recent data (e.g. Ma et al. , 2008) suggest that with respect to cancer endpoints, it is important to consider insulin levels as well as IGF-1 levels. The relationships between diet, insulin and IGF-1 levels, and clinical health outcomes is an important topic, but one that appears to be more complex than might have been implied by animal models.

Weight Loss and Maintenance Outcomes Using Moderate and Severe Caloric Restriction in an Outpatient Setting

The objective of this study was to determine if a formula diet of 520 kilocalorie (kcal, 2177 kilojoules [kJ]) compared to 850 kcal (3558 kJ) produces significantly greater weight loss and improved weight maintenance in a clinical outpatient setting. The investigation was a retrospective analysis of data from 1887 participants who underwent weight loss between December 1994 and January 2003. Participants were between the ages of 18 and 70 and completed a minimum of 12 weeks of a very-low-energy diet (VLED; 520 kcal) or a low-energy diet (LED; 850 kcal). Participants attended weekly meetings, were weighed, and received instruction in behavioral skills. Following active weight loss, participants transitioned to weight maintenance and were prescribed an individual structured meal plan aimed at maintaining body weight. Both levels of energy intake produced significant weight loss over 12 weeks (P < 0.05). Weight loss was 15.2 +/- 4.1% and 14.3 +/- 3.7% of initial body weight for participants in the VLED (n = 1231) and LED (n = 656), respectively. After controlling for baseline body weight, there was no significant difference between diets. Similarly, there was no significant difference in weight regain between VLED and LED after 12, 24, 36, and 48 weeks of weight maintenance. VLED did not produce a greater weight loss than the LED. LED provides similar weight loss with a lower incidence of adverse events and diminished need for medical monitoring. We conclude LED is an efficacious, safe, and less burdensome diet compared to VLED.

Effect of severe calorie restriction on the lung in two strains of mice

There is a body of literature in animal models that has suggested the development of emphysema following severe calorie restriction. This has led to the notion of "nutritional emphysema" that might have relevance in COPD patients. There have been few studies, however, that have looked closely at both the mechanics and lung structure in the same animals. In the present work, we examined lung mechanics and histological changes in two strains of mice that have substantial differences in alveolar size, the C57BL/6 and C3H/HeJ strains. We quantified the dynamic elastance and resistance at 2.5 Hz, the quasistatic pressure volume curve, and the alveolar chord lengths in lungs inflated to a lung capacity at 25-30 cm H(2)O. We found that after 2 or 3 wk of calorie restriction to 1/3 their normal diet, the lungs became stiffer with increased resistance. In addition, the lung capacity was also decreased. These mechanical changes were reversed after 2 wk on a normal ad libitum diet. Histology of the postmortem fixed lungs showed no changes in the mean alveolar chord lengths with calorie restriction. Although the baseline mechanics and alveolar size were quantitatively different in the two strains, both strains showed similar qualitative changes during the starvation and refeeding periods. Thus, in two strains of mice with genetically determined differences in alveolar size, neither the mechanics nor the histology show any evidence of emphysema-like changes with this severe caloric insult.

Fueling around with glycogen

Glycogen is a versatile fuel that provides energy for muscle contraction anaerobically, by substrate-level phosphorylation when glycogen is metabolized to lactic acid, and aerobically, by providing glycogen-derived pyruvate and NADH for oxidative metabolism. Both are required for normal muscle function. Anaerobic glycogenolysis is used to power muscle contractions during maximal exertion since it is able to generate ATP at more than twice the rate of oxidative phosphorylation.1 Glycogen also becomes a critical oxidative substrate in the transition from rest to exercise and in supporting maximal rates of oxidative phosphorylation.1 Glycogen depletion during sustained aerobic activities results in fatigue, and is a rationale for “glycogen loading” before endurance exercise. A survival feature of muscle glycogen is suggested by skeletal muscle lacking the enzyme glucose-6-phosphatase, thus preserving intramuscular glycogen for the energetic needs of fight or flight even in a state of severe caloric restriction,2 whereas liver glycogen is liberated as glucose to support the metabolic requirements of other tissues. A high demand for limited muscle glycogen requires tight regulation of glycogen phosphorylase, the rate-limiting …

Thematic review series: Skin Lipids. Sebaceous gland lipids: friend or foe?

Sebaceous glands are intriguing glands that are found throughout the human body except on the palms of the hands and soles of the feet. The true function of these glands has yet to be determined, but there are several theories, including antioxidant effects, antibacterial effects, and transport of pheromones. Sebaceous glands produce lipids that are involved in the pathogenesis of one of the most prevalent diseases of adolescence, acne. Although the majority of lipids produced by the sebaceous gland are also produced in other areas of the body, there are two that are characteristic of the sebaceous gland, wax esters and squalene. This review seeks to present an update on the physiology of the sebaceous glands, with particular emphasis on the production of sebaceous lipids.

Caloric restriction and refeeding promoted different metabolic effects in fat depots and impaired dyslipidemic profile in rats

Objective We investigated the effects of severe caloric restriction and refeeding with a high-fat diet on lipid uptake by visceral adipose fat and lipid profile in rats. Methods Rats were assigned to six groups: a chow diet (C), a high-fat diet (H), severe caloric restriction (SC and SH), and severe caloric restriction plus refeeding (SC-r and SH-r) during 8 wk. All animals were killed by decapitation 4 h after intragastric administration of [1- 14C] triolein (∼0.5 g, 0.3 μCi/rat). Liver; visceral retroperitoneal (RET), epididymal (EPI), and omental (VIS) white adipose tissues; brown adipose tissue; and intestine were immediately removed and weighed. The whole intestine was withdrawn and homogenized to determine lipid uptake. Total cholesterol, high-density lipoprotein (HDL), and triacylglycerol in plasma were determined enzymatically. Results The SC and SH groups showed reduced visceral adiposity, although this effect was more evident in the SC group. The SC group had greater lipid absorption in the VIS than the C group. The SH treatment increased RET and VIS lipid uptake in relation to the H group. The SH-r treatment increased RET and VIS adiposity. HDL cholesterol decreased with caloric restriction in the SC and SH groups. The SH-r treatment did not increase HDL cholesterol. Conclusion Severe caloric restriction decreased visceral adiposity even in rats in the H group but did not reduce the risk of development of dyslipidemia. Therefore, food restriction plus refeeding with a high-fat diet increase the risk of development of visceral adiposity and dyslipidemia.

Leptin Deficiency Per Se Dictates Body Composition and Insulin Action in ob/ob Mice

Obese humans are often insulin- and leptin resistant. Since leptin can affect glucose metabolism, it is conceivable that a lack of leptin signal transduction contributes to insulin resistance. It remains unclear whether leptin affects glucose metabolism via peripheral and/or central mechanistic routes. In the present study, we aimed: (i) to determine the relative contributions of lack of leptin signal transduction and adiposity to insulin resistance and (ii) to establish the impact of central leptin action on glucose metabolism. To address the first point, ob/ob mice were subjected to severe calorie restriction, so that their body weight became similar to that of wild-type mice. Insulin sensitivity was measured in obese ob/ob, lean (food restricted) ob/ob and lean, weight-matched wild-type mice. To address the second point, leptin (or vehicle) was i.c.v. infused to the lateral cerebral ventricle of ob/ob mice and insulin sensitivity was determined. Hyperinsulinaemic euglyceamic clamps were used to quantify insulin sensitivity. Food restriction barely affected body composition, although it profoundly curtailed body weight. Insulin suppressed hepatic glucose production (HGP) to a greater extent in lean ob/ob than in obese ob/ob mice, but its impact remained considerably less than in wild-type mice (% suppression: 11.8 +/- 8.9 versus 1.3 +/- 1.1 versus 56.6 +/- 13.0%/nmol, for lean, obese ob/ob and wild-type mice, respectively; P < 0.05). The insulin-mediated glucose disposal (GD) of lean ob/ob mice was also in between that of obese ob/ob and wild-type mice (37.5 +/- 21.4 versus 25.1 +/- 14.6 versus 59.6 +/- 17.3 mumol/min/kg/nmol of insulin, respectively; P < 0.05 wild-type versus obese ob/ob mice). Leptin infusion acutely enhanced both hepatic insulin sensitivity (insulin-induced inhibition of HGP) and insulin-mediated GD (9.1 +/- 2.4 versus 5.0 +/- 2.7%/nmol of insulin, and 25.6 +/- 5.6 versus 13.6 +/- 4.8 mumol/min/kg/nmol of insulin, respectively; P < 0.05 for both comparisons) in ob/ob mice. Both a lack of leptin signals and adiposity may contribute to insulin resistance in obese individuals. Diminution of central leptin signalling can critically affect glucose metabolism in these individuals.

Low-level caloric restriction rescues proteasome activity and Hsc70 level in liver of aged rats

Proteasome activity is known to decrease with aging in ad libitum (AL) fed rats. Severe caloric restriction (CR) significantly extends the maximum life-span of rats, and counteracts the age-associated decrease in liver proteasome activities. Since few investigations have explored whether lower CR diets might positively counteract the age associated decrease in proteasome activity, we then investigated the effects of a mild CR regimen on animal life-span, proteasome content and function. In addition, we addressed the question whether both CR regimens might also affect the expression of Hsc70 protein, a constitutive chaperone reported to share a role in the function of proteasome complex and in the repair of proteotoxic damage, and whose level decreased during aging. In contrast to severe CR, mild CR had a poor effect on life-span; however, it better counteracted the decrease of proteasome activities. Both regimens, however, maintain Hsc70 in liver of old rats at level comparable to that of young rats. Interestingly, the effects of aging and CRs on liver proteasome enzyme activities did not appear to be associated with parallel changes in the amount of proteasome proteins suggesting that the quality (molecular activity of the enzymes) rather than the quantity are likely to be modified with age. In conclusion, the results presented in this work show that a mild CR can have beneficial effects on liver function of aging rats because is adequate to counteract the decrease of proteasome function and Hsc70 chaperone level.

Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy

A 14-year-old boy presented with daytime somnolence, intermittent emesis and hypothyroidism. Neuroimaging revealed a calcified suprasellar intracranial mass, suspected to be a craniopharyngioma. Subtotal resection of the tumor confirmed the diagnosis. Extreme obesity (BMI >60 kg/m(2)) and hyperinsulinemia followed tumor resection and cranial irradiation. Dietary interventions were unsuccessful, and pharmacologic intervention (i.e. octreotide) only slowed the rate of weight gain. Radiography documented the suprasellar mass. Following surgical resection and radiotherapy, hypothalamic-pituitary deficiencies were found. Preprandial and postprandial excursions of insulin, active ghrelin and leptin were measured before and after gastric bypass surgery. Panhypopituitarism, hypothalamic obesity and hyperinsulinemia following craniopharyngioma therapy. Severe caloric restriction, octreotide, and pituitary hormone replacement did not produce weight loss. Gastric bypass surgery led to reduced food cravings, significant weight loss, and amelioration of obesity-related comorbidities. Correction of fasting hyperinsulinemia, normalization of postprandial insulin responses, and reductions in active ghrelin and leptin concentrations were also observed.

Effect of a caloric restriction regimen on the angiogenic capacity of aorta and on the expression of endothelin-1 during ageing

Ageing is accompanied by impaired angiogenesis, as well as by a deficient expression of several angiogenic growth factors and the alteration of endothelial functions. Caloric restriction (CR) is the only intervention that can extend lifespan and retard age-related-decline functions in mammals by reducing the rate of ageing and the progression of the associated diseases. Herein, we have investigated the effects of ageing and of a caloric restriction regimen (mild or severe) on the angiogenic response and on the expression of endothelin-1 (ET-1) in the aorta of male 3-, 12- or 24-month-old Sprague–Dawley rats fed ad libitum (AL), fed ad libitum and fasted 1 day a week (mild CR) or fasted every other in alternate days (severe CR). Our findings, using the rat aorta ring assay, show that the angiogenic capacity of aorta decreases with ageing in the oldest rats only. Furthermore, caloric restriction counteracts the age-related changes caloric restrictions actually give raise to a similar recovery. Interestingly, the mRNA ET-1 levels as well as ET-1 expression in aorta sprouting decreases both in middle and in aged animals. Mild and severe caloric restriction regimens prevents ET-1 changes.

Peroxisome Proliferator Activator Receptor γ Coactivator-1 Expression Is Reduced in Obesity

Peroxisome proliferator activator receptor-gamma coactivator 1 (PGC-1) is a major candidate gene for diabetes-related metabolic phenotypes, contributing to decreased expression of nuclear-encoded mitochondrial genes in muscle and adipose tissue. We have demonstrated that muscle expression of PGC-1alpha and -beta is reduced in both genetic (Lep(ob)/Lep(ob)) and acquired obesity (high fat diet). In C57BL6 mice, muscle PGC-1alpha expression decreased by 43% (p < 0.02) after 1 week of a high fat diet and persisted more than 11 weeks. In contrast, PGC-1alpha reductions were not sustained in obesity-resistant A/J mice. To identify mediators of obesity-linked reductions in PGC-1, we tested the effects of cellular nutrients in C2C12 myotubes. Although overnight exposure to high insulin, glucose, glucosamine, or amino acids had no effect, saturated fatty acids potently reduced PGC-1alpha and -beta mRNA expression. Palmitate decreased PGC-1alpha and -beta expression by 38% (p = 0.01) and 53% (p = 0.006); stearate similarly decreased expression of PGC-1alpha and -beta by 22% (p = 0.02) and 39% (p = 0.02). These effects were mediated at a transcriptional level, as indicated by an 11-fold reduction of PGC-1alpha promoter activity by palmitate and reversal of effects by histone deacetylase inhibition. Palmitate also (a) reduced expression of tricarboxylic acid cycle and oxidative phosphorylation mitochondrial genes and (b) reduced oxygen consumption. These effects were reversed by overexpression of PGC-1alpha or -beta, indicating PGC-1 dependence. Palmitate effects also required p38 MAPK, as demonstrated by 1) palmitate-induced increase in p38 MAPK phosphorylation, 2) reversal of palmitate effects on PGC-1 and mitochondrial gene expression by p38 MAPK inhibitors, and 3) reversal of palmitate effects by small interfering RNA-mediated decreases in p38alpha MAPK. These data indicate that obesity and saturated fatty acids decrease PGC-1 and mitochondrial gene expression and function via p38 MAPK-dependent transcriptional pathways.

Investigation of regulatory T cells in anorexia nervosa

The aim of our study was to determine, how severe calorie restriction in anorexia nervosa (AN) may influence regulatory T (Treg) cells and their cellular networks, that is, their main inducers (dendritic cells (DC) and monocytes) and their target cells, CD4+ lymphocytes. We measured the prevalence of Tregs, myeloid and plasmocytoid DC. The prevalence of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-12-positive monocytes, IL-2, IL-4 and interferon (IFN)-gamma positive CD4+ cells was determined by intracellular staining after activation. In total, 21 AN patients and 19 healthy age-matched controls (body mass index values, median (range): 14.9 (11.1-17.4) vs 23.2 (19.5-27.4) kg/m(2)) have been recruited. Prevalence of Tregs, DCs, TNF-alpha and IL-12-positive monocytes, IL-4 and IFN-gamma-producing CD4+ cells were similar in AN and controls. The prevalence of IL-2-positive CD4+ cells was somewhat lower in AN (% value, median (range): 12.05 (7.50-16.70) vs 14.40 (12.00-22.00), P<0.05). None of these parameters correlated with the patients' clinical characteristics. Our results suggest that the antigen presenting cell - regulatory T cell - CD4+ lymphocyte axis is not affected by calorie and nutritional deficiency.

Immune response after experimental allergic encephalomyelitis in rats subjected to calorie restriction

Male Lewis rats (6 weeks-old) were submitted to a calorie restriction equivalent to 33% or 66% of food restriction. Fifteen days later, groups of 7 animals were injected with complete Freund's adjuvant plus spinal cord homogenate (SCH) to induce experimental allergic encephalomyelitis (EAE) or with complete Freund's adjuvant alone. EAE was defined solely on clinical grounds. Rats were assessed daily for clinical signs of EAE and were killed on day 15 after immunization. Both diet and SCH injection diminished body weight significantly. In contrast to rats receiving a normal diet or a 33% calorie-restricted diet, rats subjected to severe calorie restriction did not exhibit clinical signs of EAE. Concomitantly with the lack of disease manifestation, 66% of calorie-restricted rats injected with SCH showed significantly less splenic and lymph node mitogenic response to concanavalin A (Con A) and a higher splenic response to lipopolysaccharide. Fewer splenic, lymph node and thymic CD4+ cells, greater numbers of splenic and lymph node CD8+ and CD4+- CD8+ cells, and fewer splenic T, B and T-B cells, and lymph node and thymic B and T-B cells were observed. There was impaired interferon (IFN)-γ production occurred in the three examined tissues. The results are compatible with the view that the acute phase of EAE can be curtailed by severe calorie restriction, presumably through impaired IFN-γ production.

Rapid significant weight loss and regional lipid deposition: Implications for insulin sensitivity

To compare regional lipid deposition and insulin sensitivity after differing weight loss strategies: very low calorie diet (VLCD) and laparoscopic adjustable gastric banding (LAGB). Thirty-nine obese women underwent anthropometry, proton magnetic resonance (MR) spectroscopy for assessment of liver fat (LFAT) and MR imaging for visceral (VAT) and subcutaneous abdominal fat volume (SAT) determination. Fasting blood was taken for insulin, glucose and free fatty acid (FFA) analysis. Measurements were repeated after 6-weeks Optifast VLCD (n = 14) or 3 months after LAGB (n = 25). Similar, significant (p < 0.001) weight loss occurred after VLCD (8%) and LAGB (9%). Both interventions induced significant (p < 0.001) and similar reductions in body mass index (BMI) and waist circumference, and in SAT and VAT (VLCD p < 0.05, LAGB p < 0.001). LFAT fell only after VLCD (p < 0.05). Plasma FFA only fell after LAGB (p < 0.05). Homeostasis model assessment (HOMA-R) improved only following VLCD (p < 0.05). No relations were detected between the changes in LFAT, VAT and SAT. The change in LFAT related to the change in HOMA-R in both interventions combined (r = 0.410, p = 0.013) and in the VLCD group (r = 0.660, p = 0.020). There was no change in relative dietary fat intake after LAGB (p = 0.11). Caloric and fat restriction for 6 weeks (VLCD) reduces weight, SAT, VAT, LFAT and HOMA-R. Less severe caloric restriction for 12 weeks (LAGB) causes significant loss of weight, VAT and SAT but no detectable change in LFAT and HOMA-R. Following weight loss, a change in LFAT is related more to changes in insulin sensitivity or dietary fat than to abdominal adiposity loss.