Fructose Component Research Articles

Effects of Consuming Beverages Sweetened with Fructose, Glucose, High-Fructose Corn Syrup, Sucrose, or Aspartame on OGTT-Derived Indices of Insulin Sensitivity in Young Adults.

(1) Background: Clinical results on the effects of excess sugar consumption on insulin sensitivity are conflicting, possibly due to differences in sugar type and the insulin sensitivity index (ISI) assessed. Therefore, we compared the effects of consuming four different sugars on insulin sensitivity indices derived from oral glucose tolerance tests (OGTT). (2) Methods: Young adults consumed fructose-, glucose-, high-fructose corn syrup (HFCS)-, sucrose-, or aspartame-sweetened beverages (SB) for 2 weeks. Participants underwent OGTT before and at the end of the intervention. Fasting glucose and insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), glucose and insulin area under the curve, Surrogate Hepatic Insulin Resistance Index, Matsuda ISI, Predicted M ISI, and Stumvoll Index were assessed. Outcomes were analyzed to determine: (1) effects of the five SB; (2) effects of the proportions of fructose and glucose in all SB. (3) Results: Fructose-SB and the fructose component in mixed sugars negatively affected outcomes that assess hepatic insulin sensitivity, while glucose did not. The effects of glucose-SB and the glucose component in mixed sugar on muscle insulin sensitivity were more negative than those of fructose. (4) Conclusion: the effects of consuming sugar-SB on insulin sensitivity varied depending on type of sugar and ISI index because outcomes assessing hepatic insulin sensitivity were negatively affected by fructose, and outcomes assessing muscle insulin sensitivity were more negatively affected by glucose.

Co-fermentation Approach of Fructose and Glucose to Ethanol from Chinese Elaeagnus angustifolia Fruit (EAF).

The soluble and fermentable carbohydrate contents was detected over 47% of glucose and fructose in Chinese Elaeagnus angustifolia fruit powder (EAF), being over 47 wt% sugar content more than that of grape. Ethanol was therefore fermented directly from EAF, and different submerged fermentation modes were comparatively employed to optimize ethanol harvest. The results indicated that glucose has certain competitive inhibition on fructose bio-utilization, as well as the EAF solid residue involved fermentation mode also hindered the fermented-ethanol titer. Pectinase addition and in situ hydrolysis seemed to assist somewhat the fermentation. The water-solute fermentation mode is preferable, and glucose and fructose components were completely consumed and converted to 80.96g/L ethanol at 87.6% ethanol yield even under tannin and pectin inhibition. The fermentation result could provide some experimental data and an approach to not only new biomass resource explores of bioethanol and alcohol beverage production, but also the technological development on valorization commercials of EAF in global draught areas.

Effect of carbohydrate-feeding strategy on the production, physiochemical changes, anti-inflammation activities of polysaccharides of Poria cocos

The aim of this research was to physiochemically characterize the structure and study the pharmaceutical benefits of the polysaccharide (PS) produced by Poria cocos using two selected carbohydrates (sucrose, and potato dextrose broth) in the in vitro culture system. A direct dosage effect was shown as sucrose- or PDB-based medium on the PS yield of Paragalago cocos. Very low-molecular-weight PS (<1 kDa) were largely synthesized by sucrose and PDB feeding. Sucrose-feeding mycelia of P. cocos results in a direct dosage effect in the fructose component in the PS. Sucrose and PDB feeding increased the glucose content but decreased the galactose content of PS. This study examined the anti-inflammatory activities of PS in lipopolysaccharide (LPS)-induced RAW264.7 macrophages. At 100 μg/mL and 50 μg/mL, PS from 10 g/L PDB- treatment, denoted as PDB 10, pretreatment showed maximal inhibition of TNF-α and IL-6 release, respectively. Mechanically, PDB10 attenuated IκB from degradation in LPS-induced macrophages, and down-regulated LPS-induced phosphorylation of ERK/AKT/p-38. PDB10 showed dose-dependent inhibition of the LPS induced TGFRII signaling pathways.

Sugar causes obesity and metabolic syndrome in mice independently of sweet taste.

Intake of sugars, especially the fructose component, is strongly associated with the development of obesity and metabolic syndrome, but the relative role of taste versus metabolism in driving preference, intake, and metabolic outcome is not fully understood. We aimed to evaluate the preference for sweet substances and the tendency to develop metabolic syndrome in response to these sugars in mice lacking functional taste signaling [P2X2 (P2X purinoreceptor 2)/P2X3 (P2X purinoreceptor 3) double knockout mice (DKO)] and mice unable to metabolize fructose (fructokinase knockout mice). Of interest, our data indicate that despite their inability to taste sweetness, P2X2/3 DKO mice still prefer caloric sugars (including fructose and glucose) to water in long-term testing, although with diminished preference compared with control mice. Despite reduced intake of caloric sugars by P2X2/3 DKO animals, the DKO mice still show increased levels of the sugar-dependent hormone FGF21 (fibroblast growth factor 21) in plasma and liver. Despite lower sugar intake, taste-blind mice develop severe features of metabolic syndrome due to reduced sensitivity to leptin, reduced ability to mobilize and oxidize fats, and increased hepatic de novo lipogenesis. In contrast to P2X2/3 DKO and wild-type mice, fructokinase knockout mice, which cannot metabolize fructose and are protected against fructose-induced metabolic syndrome, demonstrate reduced preference and intake for all fructose-containing sugars tested but not for glucose or artificial sweeteners. Based on these observations, we conclude that sugar can induce metabolic syndrome in mice independently of its sweet properties. Furthermore, our data demonstrate that the metabolism of fructose is necessary for sugar to drive intake and preference in mice.

Estimating pentose phosphate pathway activity from the analysis of hepatic glycogen 13 C-isotopomers derived from [U-13 C]fructose and [U-13 C]glucose.

The pentose phosphate pathway (PPP) is an important component of hepatic intermediary metabolism. Jin et al developed an elegant 13 C-NMR method for measuring hepatic PPP flux by quantifying the distribution of glucose 13 C-isotopomers formed from [U-13 C]glycerol. We demonstrate that this approach can be extended to exogenous [U-13 C]fructose and [U-13 C]glucose precursors by 13 C-NMR analysis of glycogen. Twelve male C57BL/6 mice fed standard chow were provided a 55/45 mixture of fructose and glucose at 30% w/v in the drinking water for 18 wk. On the evening before sacrifice, the fructose component was enriched with 20% [U-13 C]fructose for 6 mice, while the glucose component was enriched with 20% [U-13 C]glucose for the remaining 6 mice. Mice were allowed to feed and drink naturally overnight, and then, euthanized. Livers were freeze-clamped and glycogen was extracted and derivatized for 13 C NMR spectroscopy. Flux of each sugar into the PPP relative to its incorporation into glycogen was quantified from selected 13 C glycogen isotopomer ratios. Both [U-13 C]fructose and [U-13 C]glucose precursors yielded glycogen 13 C-isotopomer distributions that were characteristic of PPP activity. The fraction of [U-13 C]glucose utilized by the PPP relative to its conversion to glycogen via the direct pathway was 14 ± 1%, while that from [U-13 C]fructose relative to its conversion to glycogen via the indirect pathway was significantly lower (10 ± 1%, P = .00032). Hepatic PPP fluxes from both [U-13 C]glucose and [U-13 C]fructose precursors were assessed by 13 C NMR analysis of glycogen 13 C-isotopomers. Glucose-6-phosphate generated via glucokinase and the direct pathway is preferentially utilized by the PPP.

French Recommendations for Sugar Intake in Adults: A Novel Approach Chosen by ANSES.

This article presents a systematic review of the scientific evidence linking sugar consumption and health in the adult population performed by a group of experts, mandated by the French Agence nationale de sécurité sanitaire de l’alimentation, de l’environnement, et du travail (ANSES). A literature search was performed by crossing search terms for overweight/obesity, diabetes/insulin resistance, dyslipidemia/cardiovascular diseases, non-alcoholic fatty liver diseases (NAFLD), and uric acid concentrations on one hand and for intake of sugars on the other. Controlled mechanistic studies, prospective cohort studies, and randomized clinical trials were extracted and assessed. A literature analysis supported links between sugar intake and both total energy intake and body weight gain, and between sugar intake and blood triglycerides independently of total energy intake. The effects of sugar on blood triglycerides were shown to be mediated by the fructose component of sucrose and were observed with an intake of fructose >50 g/day. In addition, prospective cohort studies showed associations between sugar intake and the risk of diabetes/insulin resistance, cardiovascular diseases, NAFLD, and hyperuricemia. Based on these observations, ANSES proposed to set a maximum limit to the intake of total sugars containing fructose (sucrose, glucose–fructose syrups, honey or other syrups, and natural concentrates, etc.) of 100 g/day.

Fructose metabolism and metabolic disease.

Increased sugar consumption is increasingly considered to be a contributor to the worldwide epidemics of obesity and diabetes and their associated cardiometabolic risks. As a result of its unique metabolic properties, the fructose component of sugar may be particularly harmful. Diets high in fructose can rapidly produce all of the key features of the metabolic syndrome. Here we review the biology of fructose metabolism as well as potential mechanisms by which excessive fructose consumption may contribute to cardiometabolic disease.

Fructose metabolism, cardiometabolic risk, and the epidemic of coronary artery disease.

Despite strong indications that increased consumption of added sugars correlates with greater risks of developing cardiometabolic syndrome (CMS) and cardiovascular disease (CVD), independent of the caloric intake, the worldwide sugar consumption remains high. In considering the negative health impact of overconsumption of dietary sugars, increased attention is recently being given to the role of the fructose component of high-sugar foods in driving CMS. The primary organs capable of metabolizing fructose include liver, small intestine, and kidneys. In these organs, fructose metabolism is initiated by ketohexokinase (KHK) isoform C of the central fructose-metabolizing enzyme KHK. Emerging data suggest that this tissue restriction of fructose metabolism can be rescinded in oxygen-deprived environments. In this review, we highlight recent progress in understanding how fructose metabolism contributes to the development of major systemic pathologies that cooperatively promote CMS and CVD, reference recent insights into microenvironmental control of fructose metabolism under stress conditions and discuss how this understanding is shaping preventive actions and therapeutic approaches.

Pathogenesis of Cardiovascular and Metabolic Diseases: Are Fructose-Containing Sugars More Involved Than Other Dietary Calories?

There is increasing concern that sugar consumption may be linked to the development of metabolic and cardiovascular diseases. There is indeed strong evidence that consumption of energy-dense sugary beverages and foods is associated with increased energy intake and body weight gain over time. It is further proposed that the fructose component of sugars may exert specific deleterious effects due to its propension to stimulate hepatic glucose production and de novo lipogenesis. Excess fructose and energy intake may be associated with visceral obesity, intrahepatic fat accumulation, and high fasting and postprandial blood triglyceride concentrations. Additional effects of fructose on blood uric acid and sympathetic nervous system activity have also been reported, but their link with metabolic and cardiovascular diseases remains hypothetical. There is growing evidence that fructose at physiologically consumed doses may exert important effects on kidney function. Whether this is related to the development of high blood pressure and cardiovascular diseases remains to be further assessed.

Oral sucrose for heel lance enhances adenosine triphosphate use in preterm neonates with respiratory distress

Objective:To examine the effects of oral sucrose on procedural pain, and on biochemical markers of adenosine triphosphate utilization and oxidative stress in preterm neonates with mild to moderate respiratory distress.Study design:Preterm neonates with a clinically required heel lance that met study criteria (n = 49) were randomized into three groups: (1) control (n = 24), (2) heel lance treated with placebo and non-nutritive sucking (n = 15) and (3) heel lance treated with sucrose and non-nutritive sucking (n = 10). Plasma markers of adenosine triphosphate degradation (hypoxanthine, xanthine and uric acid) and oxidative stress (allantoin) were measured before and after the heel lance. Pain was measured using the Premature Infant Pain Profile. Data were analyzed using repeated measures analysis of variance, chi-square and one-way analysis of variance.Results:We found that in preterm neonates who were intubated and/or were receiving ⩾30% FiO2, a single dose of oral sucrose given before a heel lance significantly increased markers of adenosine triphosphate use.Conclusion:We found that oral sucrose enhanced adenosine triphosphate use in neonates who were intubated and/or were receiving ⩾30% FiO2. Although oral sucrose decreased pain scores, our data suggest that it also increased energy use as evidenced by increased plasma markers of adenosine triphosphate utilization. These effects of sucrose, specifically the fructose component, on adenosine triphosphate metabolism warrant further investigation.

Operant licking for intragastric sugar infusions: Differential reinforcing actions of glucose, sucrose and fructose in mice

Intragastric (IG) flavor conditioning studies in rodents indicate that isocaloric sugar infusions differ in their reinforcing actions, with glucose and sucrose more potent than fructose. Here we determined if the sugars also differ in their ability to maintain operant self-administration by licking an empty spout for IG infusions. Food-restricted C57BL/6J mice were trained 1h/day to lick a food-baited spout, which triggered IG infusions of 16% sucrose. In testing, the mice licked an empty spout, which triggered IG infusions of different sugars. Mice shifted from sucrose to 16% glucose increased dry licking, whereas mice shifted to 16% fructose rapidly reduced licking to low levels. Other mice shifted from sucrose to IG water reduced licking more slowly but reached the same low levels. Thus IG fructose, like water, is not reinforcing to hungry mice. The more rapid decline in licking induced by fructose may be due to the sugar's satiating effects. Further tests revealed that the Glucose mice increased their dry licking when shifted from 16% to 8% glucose, and reduced their dry licking when shifted to 32% glucose. This may reflect caloric regulation and/or differences in satiation. The Glucose mice did not maintain caloric intake when tested with different sugars. They self-infused less sugar when shifted from 16% glucose to 16% sucrose, and even more so when shifted to 16% fructose. Reduced sucrose self-administration may occur because the fructose component of the disaccharide reduces its reinforcing potency. FVB mice also reduced operant licking when tested with 16% fructose, yet learned to prefer a flavor paired with IG fructose. These data indicate that sugars differ substantially in their ability to support IG self-administration and flavor preference learning. The same post-oral reinforcement process appears to mediate operant licking and flavor learning, although flavor learning provides a more sensitive measure of sugar reinforcement.

Normal roles for dietary fructose in carbohydrate metabolism.

Although there are many well-documented metabolic effects linked to the fructose component of a very high sugar diet, a healthy diet is also likely to contain appreciable fructose, even if confined to that found in fruits and vegetables. These normal levels of fructose are metabolized in specialized pathways that synergize with glucose at several metabolic steps. Glucose potentiates fructose absorption from the gut, while fructose catalyzes glucose uptake and storage in the liver. Fructose accelerates carbohydrate oxidation after a meal. In addition, emerging evidence suggests that fructose may also play a role in the secretion of insulin and GLP-1, and in the maturation of preadipocytes to increase fat storage capacity. Therefore, fructose undergoing its normal metabolism has the interesting property of potentiating the disposal of a dietary carbohydrate load through several routes.

No effect of the type of sugar on ectopic fat storage (1039.1)

Dietary sugar intake has been implicated in the development of insulin resistance and subsequent cardiometabolic disease. It has been proposed the fructose component of commonly consumed sugars may promote the storage of ectopic fat deposits to a greater degree than other types of sugars. The purpose of the present study was to investigate the changes in muscle and liver fat after ten weeks of daily consumption of different types of sugars.48 weight‐stable (weight change &lt;3% in previous 30 days) individuals aged 20‐60 years old drank sugar‐sweetened low fat milk every day for 10 weeks as part of their usual diet. The amount of milk consumed was individualized for each participant based on the estimated number of calories required to maintain body weight (Miflin St Jeor equation) and random group assignment: Groups 1 and 2 ‐ 9% estimated caloric intake from fructose or glucose respectively added to milk. Groups 3 and 4 ‐ 18% of estimated caloric intake from HFCS or sucrose respectively added to the milk ( 50th percentile for consumption levels of fructose in the USA). Whole body fat percentage was measured by DEXA (GE Lunar) while muscle fat was measured by MRI and liver fat content was measured by MRS (Siemens 3T Skyra).There was a small increase in weight (166.7 ± 29.4 vs 169.0 ± 31.2lbs, p&lt;0.01) and body fat percentage (32.6 ± 8.9 vs 33.1 ±8.4%, p&lt;0.05) in the entire cohort, but there was no effect of the type of sugar consumed. Small increases were also observed in the vastus lateralis (2.7 ± 0.9 vs 3.1 ±1.2 g/dl, p&lt;0.01) and gluteus maximus (3.6 ±1.1 vs 4.3 ±1.6 g/dl, p&lt;0.001) and in the liver (4.1 ±5.4 vs 4.9 ±6.1 %, p&lt;0.01), but none of these changes were affected by the type of sugar consumed.These data suggest that short‐term changes in overall body composition are also reflected in the fat content of the liver and muscles, even when the changes are small. Furthermore, in the context of overall fat gain, whether or not the sugar contained fructose had no impact on the magnitude of change.

Abstract 19: Stimulatory Effects of Fructose vs. Glucose on Brain Reward Activation and Hunger are Heightened in Obese Young Adults

Increases in consumption of sugar-sweeteners are linked to obesity, diabetes and cardiovascular disease. Studies by our group and others suggest that the fructose component of sugar-sweeteners may act centrally to promote overeating behavior. Using functional magnetic resonance imaging (fMRI), we previously demonstrated that, unlike glucose, fructose ingestion failed to reduce neuronal activity in brain appetite and reward regions and failed to increase satiety in normal-weight adults. The objective of this study was to test the hypothesis that fructose compared to glucose ingestion would cause greater food-cue reactivity in brain reward areas and greater hunger, and that these differential effects would be heightened in obese compared to lean individuals. This study is part of a larger ongoing double-blinded, random-order crossover study on brain, hormone and appetitive responses to acute consumption of drinks containing 75 grams (300kcal) fructose or an equivalent dose of glucose. fMRI scans were performed using a 3-Tesla scanner on 13 participants, 5 obese (3 female,2 male; age 22±2, BMI 37±3.8) and 8 lean (3 female,5 male; age 21±2, BMI 22.8±1.7). Scanning was performed while participants viewed images of high-calorie food pictures and non-food items using a block design. Appetite scales were obtained before and 60 min after drink ingestion. Blood-oxygen level dependent (BOLD) sequences were used to measure brain responses to food and non-food cues after drink ingestion. Paired-t tests were performed to examine drink effects on BOLD responses to high-calorie food vs. non-food cues and hunger responses. Obese vs. lean comparison of drink effects were analyzed using independent samples T-tests. In the total group, fructose vs. glucose ingestion resulted in greater activation of the amygdala (9.1±4, p=.045) and the nucleus accumbens (11.4±6, p=.07), brain regions that mediate reward and pleasure. There were no significant differences in baseline hunger ratings between sessions. However, hunger ratings were significantly greater after consumption of fructose compared to glucose (1.9±0.6, p=.011). Body mass index (BMI) group interactions were seen with drink condition. Amygdala activation was significantly greater after fructose vs. glucose ingestion in the obese group (t(1,4)=4.406, p=0.01), but not the lean group (t(1,7)=0.754, p=0.48). Ratings of hunger tended to be higher after fructose vs. glucose ingestion in the obese compared to the lean group but the differences were not statistically significant with this sample size (p=0.15). In conclusion, these results demonstrate that acute consumption of fructose compared to glucose results in greater brain reward activation to high-calorie food cues and increased hunger. These disparate responses to fructose vs. glucose ingestion were heightened in obese individuals and may play a role in promoting overeating behavior.

Challenging the fructose hypothesis: new perspectives on fructose consumption and metabolism.

The field of sugar metabolism, and fructose metabolism in particular, has experienced a resurgence of interest in the past decade. The “fructose hypothesis” alleges that the fructose component common to all major caloric sweeteners (sucrose, high-fructose corn syrup, honey, and fruit juice concentrates) plays a unique and causative role in the increasing rates of cardiovascular disease, hypertension, diabetes, cancer, and nonalcoholic fatty liver disease. This review challenges the fructose hypothesis by comparing normal U.S. levels and patterns of fructose intake with contemporary experimental models and looking for substantive cause-and-effect evidence from real-world diets. It is concluded that 1) fructose intake at normal population levels and patterns does not cause biochemical outcomes substantially different from other dietary sugars and 2) extreme experimental models that feature hyperdosing or significantly alter the usual dietary glucose-to-fructose ratio are not predictive of typical human outcomes or useful to public health policymakers. It is recommended that granting agencies and journal editors require more physiologically relevant experimental designs and clinically important outcomes for fructose research.

Boissons sucrées et obésité: aspects épidémiologiques et physiopathologiques

Consumption of sugar-sweetened beverages (SSB) has markedly increased over the past decades, and several authors have suggested that such increase may be causal to the present obesity epidemic. Consumption of SSB is positively associated with body weight gain. However, the strength of this association markedly differs by age: adolescents, who represent the highest consumer group, show the strongest association, while this effect is more moderate in infants/toddlers and seniors. SSB contain two simple sugars, found in similar quantities: glucose and fructose. Bound together, they form the disaccharide sucrose. Up to now, most of the deleterious effects of SSB have been attributed to the fructose component, due to its particular metabolism. Such effects include regulation of food intake, increased visceral fat deposition, increased hepatic lipid accumulation and circulating triglycerides. However, recent evidences suggest that when administered in hypercaloric condition, glucose may have as deleterious effects as fructose. This review aims at characterizing SSB consumption over various age classes in France and the US, as well as physiological mechanisms involved in the development of obesity and related metabolic diseases.

Comparative study of cocoa-sweat and that of pure honey

The comparative study of cocoa-sweat and that of pure honey were carried out to show whether the taste of former could be accepted as an alternative to the later, using the hedonic scale of sensory evaluation. The fructose components of cocoa-sweat were compared with that of pure honey, using spectrophotometer absorbency method. The cocoa-sweat concentrated for 10 min had a closed value of fructose content (2.69%) as against 3.41% of pure honey. The cocoa-sweat concentrated for 20 and 30 min had higher fructose content of 9.31 and 9.46% respectively, as against 3.41% of pure honey. From the sensory evaluation tests, the cocoa-sweat concentrated for 20 and 30 min were highly acceptable with mean values if 27.3 and 28.8 respectively, as compared to the sweat concentrated for 10 min that had 24.6 mean value. The sweat concentrated for 10 min was recommended for use as a natural source of sweetener in place of sugar, in the absence of pure honey.

Sugary drinks in the pathogenesis of obesity and cardiovascular diseases

Soft drink overconsumption is now considered to be a major public health concern with implications for cardiovascular diseases. This follows a number of studies performed in animals suggesting that chronic consumption of refined sugars can contribute to metabolic and cardiovascular dysregulation. In particular, the monosaccharide fructose has been attracting increasing attention as the more harmful sugar component in terms of weight gain and metabolic disturbances. High-fructose corn syrup is gradually replacing sucrose as the main sweetener in soft drinks and has been blamed as a potential contributor to the current high prevalence of obesity. There is also considerable evidence that fructose, rather than glucose, is the more damaging sugar component in terms of cardiovascular risk. This review focuses on the potential role of sugar drinks, particularly the fructose component, in the pathogenesis of obesity and cardiovascular diseases.

Thermodynamic Properties and Kinetics of the Physical Ageing of Amorphous Glucose, Fructose, and Their Mixture

The physical ageing characteristics of glucose, fructose, and their mixtures were studied using standard differential scanning calorimetry (DSC). The inflection, onset, midpoint,half-height, and endpoint glass transition temperature (Tg), fictive temperature (Tf), and relaxation enthalpy (ΔH) were measured as a function of ageing time. The relationship between ΔH and Tf was evaluated. The time dependence of ΔH was fit using the Cowie and Ferguson model. The ageing rate was expressed in terms of the average relaxation time ( ) and the entropy production (P). It was found that the fructose component decreased the rate of ageing of the mixtures.

Overnutrition in spiny mice (Acomys cahirinus): beta-cell expansion leading to rupture and overt diabetes on fat-rich diet and protective energy-wasting elevation in thyroid hormone on sucrose-rich diet.

The investigation of diabetes propensity in spiny mice, performed in Geneva and Jerusalem colonies, is reviewed. Spiny mice live in semi-desert regions of the eastern Mediterranean countries. Those transferred to Geneva in the 1950s were maintained on a rodent diet supplemented by fat-rich seeds. They became obese, exhibited pancreatic islet hyperplasia and hypertrophy. Low insulin secretion response was characteristic of this species, despite ample pancreatic content of insulin. After a few months, diabetes with ketosis occurred, often suddenly, in association with islet cell disintegration. In Jerusalem the spiny mice were collected from their native habitat and placed on diets containing 50% sucrose or fat-rich seed diets. On a sucrose-rich diet, spiny mice developed hepatomegaly, lipogenic enzyme hyperactivity, and elevation in very low density lipoproteins as a result of metabolism of the fructose component mainly in the liver. No overt diabetes or pancreatic islet disintegration were observed, although insulin content and beta-cell hypertrophy and hyperplasia were apparent. On a fat-rich diet, spiny mice exhibited marked weight gain, adipose tissue growth and low hepatic lipogenesis. The obesity was accompanied by mild hyperglycemia and hyperinsulinemia with glucose intolerance leading to an occasional glucosuria after several months on the diet. The sucrose diet induced an extrathyroidal elevation of triiodothyronine (T(3)). Serum T(3) level and hepatic T(4)-T(3) conversion were increased, while serum T(4) levels tended to decrease. The activity of the T(3)-inducible hepatic mitochondrial FAD-glycerophosphate oxidase and K(+)/Na(+)-ATPase, as well as body temperature were increased, indicating that the sucrose diet was associated with enhanced thermogenesis and energy-wasting metabolic cycling. The sucrose-rich diet might exert an adaptive thermogenesis-mediated defense mechanism, protecting against excessive weight gain and disruptive pancreatic islet lesion. After 18 months maintenance on sucrose-rich versus fat-rich diets the number of animals surviving was significantly higher on the sucrose diet whereas on the fat diet a significant number of animals succumbed to expansive islet cell disruption and diabetes.