Caloric Restriction Paradoxically Increases Adiposity in Mice With Genetically Reduced Insulin

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2724-2734 ◽  
Author(s):  
Derek A. Dionne ◽  
Søs Skovsø ◽  
Nicole M. Templeman ◽  
Susanne M. Clee ◽  
James D. Johnson
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Caloric Restriction ◽  
Gene Dosage ◽  
Tissue Growth ◽  
Tissue Mass ◽  
Brown Adipose ◽  
Paradoxical Effects ◽  
Plasma Insulin Levels ◽  
Ad Libitum

Antiadiposity effects of caloric restriction (CR) are associated with reduced insulin/IGF-1 signaling, but it is unclear whether the effects of CR would be additive to genetically reducing circulating insulin. To address this question, we examined female Ins1+/−:Ins2−/− mice and Ins1+/+:Ins2−/− littermate controls on either an ad libitum or 60% CR diet. Although Igf1 levels declined as expected, CR was unable to reduce plasma insulin levels in either genotype below their ad libitum-fed littermate controls. In fact, 53-week-old Ins1+/−:Ins2−/− mice exhibited a paradoxical increase in circulating insulin in the CR group compared with the ad libitum-fed Ins1+/−:Ins2−/− mice. Regardless of insulin gene dosage, CR mice had lower fasting glucose and improved glucose tolerance. Although body mass and lean mass predictably fell after CR initiation, we observed a significant and unexpected increase in fat mass in the CR Ins1+/−:Ins2−/− mice. Specifically, inguinal fat was significantly increased by CR at 66 weeks and 106 weeks. By 106 weeks, brown adipose tissue mass was also significantly increased by CR in both Ins1+/−:Ins2−/− and Ins1+/+:Ins2−/− mice. Interestingly, we observed a clear whitening of brown adipose tissue in the CR groups. Mice in the CR group had altered daily energy expenditure and respiratory exchange ratio circadian rhythms in both genotypes. Multiplexed analysis of circulating hormones revealed that CR was associated with increased fasting and fed levels of the obesogenic hormone, glucose-dependent insulinotropic polypeptide. Collectively these data demonstrate CR has paradoxical effects on adipose tissue growth in the context of genetically reduced insulin.

Plasticity in food intake, thermogenesis and body mass in the tree shrew (Tupaia belangeri) is affected by food restriction and refeeding

2016 ◽  
Vol 66 (2) ◽  
pp. 201-217 ◽  
Author(s):  
Wen-rong Gao ◽  
Wan-long Zhu ◽  
Fang-yan Ye ◽  
Mu-lin Zuo ◽  
Zheng-kun Wang
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Body Mass ◽  
Food Restriction ◽  
Uncoupling Protein ◽  
Tissue Mass ◽  
Serum Leptin ◽  
Brown Adipose ◽  
Ad Libitum

Physiological adjustments are important strategies for small mammals in response to variation in food availability. To determine the physiological mechanisms affected by food restriction and refeeding, tree shrews were restricted to 85% of initial food intake for 4 weeks and refedad libitumfor another 4 weeks. Changes in food intake, body mass, thermogenesis, body composition, mitochondrial cytochromecoxidase activity, uncoupling protein-1 content in brown adipose tissue and serum leptin levels were measured. The results showed that body mass, body fat mass and serum leptin levels significantly decreased in food restricted tree shrews, and increased when the restriction ended, showing a short “compensatory growth” rather than over-weight or obesity compared withad libitumcontrols. Resting metabolic rate, non-shivering thermogenesis, brown adipose tissue mass (mg), and uncoupling protein-1 content decreased significantly in response to food restriction, and returned to the control levels after the animals were refedad libitum, while the brown adipose tissue mass (%) and cytochromecoxidase activity remained stable during food restriction and refeeding. Food intake increased shortly after refeeding, which perhaps contributed to the rapid regaining of body mass. These results suggest thatTupaia belangerican adjust the status of its physiology integratively to cope with the lack of food by means of decreasing body mass, thermogenesis and serum leptin levels. Leptin may act as a starvation signal to predominantly mediate the reduction in body mass and energy expenditure.

Effects of fasting and food restriction on brown adipose tissue composition in normal and dystrophic hamsters

1986 ◽  
Vol 64 (7) ◽  
pp. 970-975 ◽  
Author(s):  
M. Desautels ◽  
R. A. Dulos ◽  
H. M. Yuen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Food Deprivation ◽  
Food Restriction ◽  
Tissue Mass ◽  
Tissue Protein ◽  
Guanosine Diphosphate ◽  
Isolated Mitochondria ◽  
Daily Food ◽  
Brown Adipose

Fasting for 36–48 h or food restriction (30% reduction of daily food intake for 6 weeks) caused brown adipose tissue (BAT) atrophy in hamsters. Fasting-induced atrophy was characterized by reductions in tissue mass, DNA, protein, and thermogenin. By contrast, food restriction had no effect on tissue cellularity (DNA) but markedly reduced the tissue protein and thermogenin contents. The concentration of thermogenin in isolated mitochondria was unchanged by fasting or food restriction. Dystrophic hamsters had a reduced BAT mass when compared with weight-matched control hamsters. This resulted from a reduction in tissue cellularity since BAT DNA, protein and thermogenin contents were all reduced. The extent of binding of [3H]guanosine diphosphate to isolated mitochondria and their content of thermogenin were similar in normal and dystrophic hamsters. In response to cold exposure, as in normal hamsters, BAT of dystrophic hamsters grew and the tissue thermogenin increased, but the mitochondrial concentration of thermogenin did not change. In response to fasting, in contrast with normal hamsters, there was no significant reduction in BAT DNA in dystrophic animals and the loss of tissue protein was reduced. However, the relative changes in BAT composition during chronic food restriction were similar in normal and dystrophic animals. Thus, reduction in hamster BAT thermogenic capacity during food deprivation may occur by loss of cells and (or) reduction in the tissue protein and thermogenin contents. The extent of protein and (or) DNA loss may be dependent upon the original tissue mass and the severity of food deprivation.

Hypothalamic obesity, brown adipose tissue, and sympathoadrenal activity in rats

1985 ◽  
Vol 248 (5) ◽  
pp. E607-E617 ◽  
Author(s):  
J. G. Vander Tuig ◽  
J. Kerner ◽  
D. R. Romsos
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Heat Production ◽  
Adult Rats ◽  
Guanosine Diphosphate ◽  
Bat Mitochondria ◽  
Sympathoadrenal Activity ◽  
Brown Adipose ◽  
Energy Retention ◽  
Ad Libitum

Obesity-producing, hypothalamic knife cuts and ventromedial hypothalamic (VMH) lesions in ad libitum-fed adult rats increased intake of a high-fat diet (123 and 130%) and energy retention (880 and 1,099%) during the 4-wk period postsurgery; even when pair fed to control rats, energy retention of the knife-cut and lesioned rats was still elevated (105 and 155%). Thermogenic capacity of brown adipose tissue (BAT), estimated from guanosine diphosphate (GDP) binding to BAT mitochondria, was unchanged in hyperphagic knife-cut and VMH-lesioned rats and was reduced approximately 50% when these rats were pair fed to controls. Urinary excretion of norepinephrine (NE) was approximately twofold higher in ad libitum-fed, knife-cut, and lesioned rats than in control rats; restriction of energy intake decreased NE excretion to control values. Rates of NE turnover in heart paralleled urinary NE excretion, whereas NE turnover in BAT was generally not increased in the hyperphagic rats. Urinary epinephrine excretion, an index of adrenal medullary activity, was depressed in all knife-cut and VMH-lesioned rats. Hyperphagia coupled with a lack of increased heat production in BAT causes gross obesity in ad libitum-fed, knife-cut, and VMH-lesioned rats, whereas obesity in pair-fed rats develops in part at least as a result of reduced heat production by BAT.

scholarly journals GDP binding to brown-adipose-tissue mitochondria of mice treated chronically with corticosterone

1983 ◽  
Vol 214 (1) ◽  
pp. 265-268 ◽  
Author(s):  
K S Galpin ◽  
R G Henderson ◽  
W P T James ◽  
P Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cytochrome Oxidase ◽  
Oxidase Activity ◽  
Cytochrome Oxidase Activity ◽  
Acute Response ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
Ad Libitum ◽  
Stimulation Of

Cytochrome oxidase activity and mitochondrial GDP binding were decreased in brown adipose tissue of mice treated chronically with corticosterone. These changes occurred both in corticosterone-treated mice fed ad libitum and in treated mice pair-fed to control animals. Although the dietary stimulation of brown-adipose-tissue thermogenesis was suppressed by corticosterone, the acute response to cold was not affected.

Brown adipose tissue of cafeteria-fed rats

1981 ◽  
Vol 241 (2) ◽  
pp. E116-E120 ◽  
Author(s):  
J. Himms-Hagen ◽  
J. Triandafillou ◽  
C. Gwilliam
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Tissue Growth ◽  
Total Protein Content ◽  
Chow Diet ◽  
Control Mechanisms ◽  
Purine Nucleotides ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Wet Weight

Feeding a "cafeteria" diet for 2 wk to male Holtzman rats resulted in a weight gain that was, on average, only slightly more than that of control rats fed a regular chow diet. Wet weight, DNA, and total protein content of interscapular brown adipose tissue were more than doubled in the cafeteria-fed rats and proliferation of mitochondria paralleled tissue growth. After 2 wk of recovery from cafeteria feeding, the expanded size of the tissue had completely regressed to a normal level. Brown adipose tissue mitochondria of cafeteria-fed rats bound 3 times more purine nucleotides than mitochondria of chow-fed control rats, but no change in the proportion of polypeptides with molecular weight in the region of 32,000 could be detected. The changes in brown adipose tissue and its mitochondria in cafeteria-fed rats correspond to those seen previously in noradrenaline-treated rats, i.e., tissue growth accompanied by mitochondrial proliferation and an unmasking of proton conductance pathways. The increase in 32,000-mol-wt polypeptides seen in brown adipose tissue mitochondria of cold-acclimated rats does not occur in the cafeteria-fed rats. Control mechanisms are presumed to differ, either quantitatively or qualitatively, in the two situations, cold exposure and overeating, which both cause growth of brown adipose tissue.

scholarly journals Brown adipose tissue volume and 18F-fluorodeoxyglucose uptake are not associated with energy intake in young human adults

2019 ◽  
Vol 111 (2) ◽  
pp. 329-339 ◽  
Author(s):  
Guillermo Sanchez-Delgado ◽  
Francisco M Acosta ◽  
Borja Martinez-Tellez ◽  
Graham Finlayson ◽  
Catherine Gibbons ◽  
...  
Keyword(s):  
Young Adults ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Energy Intake ◽  
Appetite Regulation ◽  
Fdg Uptake ◽  
Brown Adipose ◽  
Ad Libitum ◽  
18F Fdg ◽  
Meal Consumption

ABSTRACT Background Several studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously examined. Objectives We aimed to investigate the associations of BAT volume and 18F-fluordeoxyglucose (18F-FDG) uptake after a personalized cold exposure with energy intake and appetite-related sensations in young healthy humans. Methods A total of 102 young adults (65 women; age: 22.08 ± 2.17 y; BMI: 25.05 ± 4.93 kg/m 2) took part in this cross-sectional study. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by means of static 18F-FDG positron-emission tomography and computed tomography scans after a 2-h personalized exposure to cold. Energy intake was estimated via an objectively measured ad libitum meal and three nonconsecutive 24-h dietary recalls. Appetite-related sensations (i.e., hunger and fullness) were recorded by visual analog scales before and after a standardized breakfast (energy content = 50% of basal metabolic rate) and the ad libitum meal. Body composition was assessed by a whole-body DXA scan. Results BAT volume and 18F-FDG uptake were not associated with quantified ad libitum energy intake (all P > 0.088), nor with habitual energy intake estimated from the 24-h dietary recalls (all P  > 0.683). Lean mass was positively associated with both the energy intake from the ad libitum meal (β: 17.612, R2 = 0.213; P < 0.001) and the habitual energy intake (β: 16.052, R2 = 0.123; P = 0.001). Neither the interaction BAT volume × time elapsed after meal consumption nor that of BAT 18F-FDG uptake × time elapsed after meal consumption had any significant influence on appetite-related sensations after breakfast or after meal consumption (all P > 0.3). Conclusions Neither BAT volume, nor BAT 18F-FDG uptake after cold stimulation, are related to appetite regulation in young adults. These results suggest BAT plays no important role in the regulation of energy intake in humans. This trial was registered at clinicaltrials.gov as NCT02365129.

scholarly journals Physiological modulation of the uptake and fate of glucose in brown adipose tissue

1993 ◽  
Vol 295 (1) ◽  
pp. 171-176 ◽  
Author(s):  
M C Sugden ◽  
M J Holness
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Brown Adipose Tissue ◽  
Fatty Acid Synthesis ◽  
Diurnal Cycle ◽  
Acid Synthesis ◽  
Pregnant Rats ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Ad Libitum

Glucose utilization indices (GUI values) and rates of fatty acid synthesis in interscapular brown adipose tissue (IBAT) varied during the diurnal cycle in virgin and late-pregnant rats permitted unrestricted access to food. In virgin rats, peak GUI values and lipogenic rates were observed at the end of the dark (feeding) phase, but were not sustained during the light phase. Whereas peak GUI values were comparable with those observed during re-feeding after 24 h starvation, maximum rates of IBAT fatty acid synthesis in virgin rats during the diurnal cycle were only approx. 25% of those measured during re-feeding after 24 h starvation. Despite hyperphagia, GUI values during the diurnal cycle in late-pregnant rats fed ad libitum were generally lower than those of age-matched virgin controls. The percentage of pyruvate dehydrogenase complex present in the active form (PDHa) was also significantly decreased. Suppression of GUI and PDHa was not parallelled by suppression of fatty acid synthesis. IBAT GUI values in late-pregnant rats during chow re-feeding ad libitum after 24 h starvation were only 25% of those of corresponding virgin controls, and stimulation of fatty acid synthesis was also dramatically attenuated. The suppression of IBAT GUI values after re-feeding in pregnancy was not due to depletion of GLUT 4 protein. The results are discussed in relation to the importance of glucose as a precursor for fatty acid synthesis in IBAT.

Relationship of brown adipose tissue with growth and obesity differences in genetically selected mouse lines

1984 ◽  
Vol 26 (3) ◽  
pp. 339-347 ◽  
Author(s):  
A. M. Saxton ◽  
E. J. Eisen ◽  
J. M. Leatherwood
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Single Gene ◽  
Tissue Growth ◽  
Growth Patterns ◽  
High Fat ◽  
Polygenic Control ◽  
Brown Adipose ◽  
Diet Induced Thermogenesis

A recent hypothesis considers brown adipose tissue (BAT) to be an important source of diet-induced thermogenesis (DIT). In turn, DIT and thermogenesis in general are believed to be key factors in the control of obesity of laboratory rodents. This hypothesis was developed from the study of single gene mutant obese rodents. The present research tested this hypothesis in mice with polygenic control of growth and obesity, which is more characteristic of the type of genetic variation expected in human and other mammalian populations. Control and high fat diets were used to test responses of five genetically selected lines of mice showing different patterns of growth and obesity. All lines deposited more fat on the high fat diet, but the most obese line showed the largest increase in BAT and the lipid-free dry (LFD) component of BAT. Use of LFD per unit body weight gave results which supported the hypothesis being tested, but it was argued that this measure is misleading. When brown and white adipose tissue growth relative to body weight were examined, 2 of the 10 line – diet groups showed alterations in BAT growth patterns. However, it was concluded that BAT, if involved at all, was not a major factor in growth and obesity differences.Key words: obesity, polygenes, adipose tissue, quantitative inheritance, mouse.

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