Distribution Of Fat Depots Research Articles

Adipose Tissue and Metabolic Health.

In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health and highlight some recent developments in understanding and exploiting adipocyte biology. Adipose tissue plays critical roles in the regulation of systemic glucose and lipid metabolism and secretes bioactive molecules possessing endocrine, paracrine, and autocrine functions. Dysfunctional adipose tissue has a detrimental impact on metabolic health and is intimately involved in key aspects of metabolic diseases such as insulin resistance, lipid overload, inflammation, and organelle stress. Differences in the distribution of fat depots and adipose characteristics relate to divergent degrees of metabolic dysfunction found in metabolically healthy and unhealthy obese individuals. Thermogenic adipocytes increase energy expenditure via mitochondrial uncoupling or adenosine triphosphate-consuming futile substrate cycles, while functioning as a metabolic sink and participating in crosstalk with other metabolic organs. Manipulation of adipose tissue provides a wealth of opportunities to intervene and combat the progression of associated metabolic diseases. We discuss current treatment modalities for obesity including incretin hormone analogs and touch upon emerging strategies with therapeutic potential including exosome-based therapy, pharmacological activation of brown and beige adipocyte thermogenesis, and administration or inhibition of adipocyte-derived factors.

Compromised browning in white adipose tissue of ageing people.

Adipose tissue plays a pivotal role in the pathology of metabolic disorders. In the past decade, brown and brown-like adipose tissues were detected in adult humans and show therapeutic potential in ageing-related metabolic diseases. This study investigated expressions of major brown adipose markers in white adipose tissue (WAT) of different ages. Their associations with metabolic parameters and key adipokines were interrogated. Cross-sectional study, 2019-2021. We recruited 21 young, 67 middle-aged, and 34 older patients. Omental adipose tissues were collected, and expressions of key brown markers and adipokines and the adipocyte size were evaluated. The fat depot distribution was evaluated by computed tomography. UCP1 and PRDM16 mRNA expressions declined with ageing in WAT and were more associated with age, than with the body mass index (BMI). The increased visceral adipose tissue (VAT) amount, as well as the VAT to subcutaneous adipose tissue (SAT) ratio, was decreased in the highest tertile of UCP1 expression, while individuals in different PRDM16 mRNA tertiles exhibited similar fat distribution. UCP1 mRNA was positively correlated with ADIPOQ and the strength of the correlation declined with ageing. In contrast, the association between UCP1 and LEP was insignificant in young and middle-aged groups but became significantly correlated in the older-people group. We also found a positive correlation between UCP1 and PRDM16. PRDM16 and UCP1, despite their key functions in adipose browning, exhibit differential clinical correlations with metabolic features in human WAT in an age-dependent manner. These two genes may participate in the pathogenesis of ageing-related metabolic diseases, but with distinct mechanisms.

Sex Hormones and Macronutrient Metabolism

The biological differences between males and females are determined by a different set of genes and by a different reactivity to environmental stimuli, including the diet, in general. These differences are further emphasized and driven by the exposure to a different hormone flux throughout the life.These differences have not been taken into appropriate consideration by the scientific community. Nutritional sciences are not immune from this “bias” and when nutritional needs are concerned, females are considered only when pregnant, lactating or when their hormonal profile is returning back to “normal,” i.e., to the male-like profile.The authors highlight some of the most evident differences in aspects of biology that are associated with nutrition.This review presents and describes available data addressing differences and similarities of the “reference man” vs. the “reference woman” in term of metabolic activity and nutritional needs. According to this assumption, available evidences of sex-associated differences of specific biochemical pathways involved in substrate metabolism are reported and discussed. The modulation by sexual hormones affecting glucose, amino acid and protein metabolism and the metabolization of nutritional fats and the distribution of fat depots, is considered targeting a tentative starting up background for a gender concerned nutritional science.

Mouse models of inherited lipodystrophy

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes and underpins the strong association between obesity and diabetes. Paradoxically, the metabolic consequences of having 'too much' fat (obesity) are remarkably similar to those of having 'too little' fat (lipodystrophy): a finding that has generated considerable interest in a rare disease. In both cases, excess energy accumulates as lipid in ectopic sites such as the liver (fatty liver) and skeletal muscle, where it plays a central role in the pathogenesis of insulin resistance, dyslipidemia and type 2 diabetes. Human lipodystrophies are characterised by a total or partial deficiency of body fat, and may be inherited or acquired in origin. Genetically engineered mice with generalised lipodystrophy manifest many of the features of the human disorder, including hyperphagia, fatty liver, hypertriglyceridaemia, insulin resistance and type 2 diabetes, providing a useful tractable model of the human disorder. Partial lipodystrophy, which causes similar, albeit milder, metabolic problems in humans has been more difficult to mimic in the mouse. This review discusses key translational studies in mice with generalised lipodystrophy, including fat transplantation and the use of recombinant leptin replacement therapy. These studies have been instrumental in advancing our understanding of the underlying molecular pathogenesis of ectopic lipid accumulation and insulin resistance, and have prompted the initiation and subsequent adoption of leptin replacement therapy in human lipodystrophies. This review also considers the possible reasons for the apparent difficulties in generating mouse models of partial lipodystrophy, such as interspecies differences in the distribution of fat depots and the apparent lack of sexual dimorphism in fat mass and distribution in mice compared with the dramatic differences present in adult humans.

Impact of Variation in the FTO Gene on Whole Body Fat Distribution, Ectopic Fat, and Weight Loss

Polymorphisms in the fat mass- and obesity-associated (FTO) gene have been identified to be associated with obesity and diabetes in large genome-wide association studies. We hypothesized that variation in the FTO gene has an impact on whole body fat distribution and insulin sensitivity, and influences weight change during lifestyle intervention. To test this hypothesis, we genotyped 1,466 German subjects, with increased risk for type 2 diabetes, for single-nucleotide polymorphism rs8050136 in the FTO gene and estimated glucose tolerance and insulin sensitivity from an oral glucose tolerance test (OGTT). Distribution of fat depots was quantified using whole body magnetic resonance (MR) imaging and spectroscopy in 298 subjects. Two-hundred and four subjects participated in a lifestyle intervention program and were examined after a follow-up of 9 months. In the cross-sectional analysis, the A allele of rs8050136 in FTO was associated with a higher BMI, body fat, and lean body mass (all P < 0.001). There was a significant effect of variation in the FTO gene on subcutaneous fat (P < or = 0.05) and a trend for liver fat content, nonvisceral adipose tissue, and visceral fat (all P < or = 0.1). However, the single-nucleotide polymorphism was not associated with insulin sensitivity or secretion independent of BMI (all P > 0.05). During lifestyle intervention, there was also no influence of the FTO polymorphism on changes in body weight or fat distribution. In conclusion, despite an association with BMI and whole body fat distribution, variation in the FTO locus has no effect on the success of a lifestyle intervention program.

Reversal of visceral adiposity in candy-diet fed female Wistar rats by the CB1 receptor antagonist rimonabant

The severity of obesity is often more determined by the distribution of fat depots rather than by body weight itself. Therefore, the effect of rimonabant on fat distribution pattern was investigated in female candy-fed Wistar rats. Female Wistar rats were fed a high fat, high carbohydrate (candy-) diet for 12 weeks. During the last 6 weeks rats were treated with rimonabant. Food intake and body weight development were investigated, as well as effects on total body fat, especially visceral fat and ectopic lipid accumulation in skeletal muscle and liver, determined by in vivo magnetic resonance imaging/magnetic resonance spectroscopy. Candy-diet increased body weight, which was predominantly due to the increased total fat mass with predominance of visceral fat accumulation. Treatment with rimonabant fully reversed the weight gain and fat deposition in the visceral cavity and skeletal muscle, in contrast to pair feeding. In spite of an only transient reduction of food intake, body weight reduction, as well as normalized body fat, reduced visceral fat and intramyocellular lipids were maintained over the treatment period. We conclude that additional factors other than reduced caloric intake must be responsible for the improvements in these lipid parameters. The complete cluster of results is consistent with increased lipid oxidation caused by rimonabant.

Adiponectin in human cord blood: relation to fetal birth weight and gender

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The aim of this study was to examine whether adiponectin is present in human fetal blood, to define its association with fetal birth weight, and to evaluate whether dynamic changes in adiponectin levels occur during the early neonatal period. Cord blood adiponectin levels were extremely high (71.0 21.0 g/ml; n 51) compared with serum levels in children and adults and positively correlated with fetal birth weights (r 0.4; P < 0.01). No significant differences in adiponectin levels were found between female and male neonates. In addition, there was no correlation between cord adiponectin levels and maternal body mass index, cord leptin, or insulin levels. Cord adiponectin levels were significantly higher compared with maternal levels at birth (61.1 19.0 vs. 17.6 4.9 g/ml; P < 0.001; n 17), and no correlation was found between cord and maternal adiponectin levels. There were no significant differences between adiponectin levels at birth and 4 d postpartum (61.1 19.0 vs. 63.8 22.0 g/ml; n 17). These findings indicate that adiponectin in cord blood is derived from fetal and not from placental or maternal tissues. The high adiponectin levels in newborns compared with adults may be due to lack of negative feedback on adiponectin production resulting from lack of adipocyte hypertrophy, low percentage of body fat, or a different distribution of fat depots in the newborns. (J Clin Endocrinol Metab 88: 5656 –5660, 2003)

Adiponectin in human cord blood: relation to fetal birth weight and gender.

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The aim of this study was to examine whether adiponectin is present in human fetal blood, to define its association with fetal birth weight, and to evaluate whether dynamic changes in adiponectin levels occur during the early neonatal period. Cord blood adiponectin levels were extremely high (71.0 +/- 21.0 microg/ml; n = 51) compared with serum levels in children and adults and positively correlated with fetal birth weights (r = 0.4; P < 0.01). No significant differences in adiponectin levels were found between female and male neonates. In addition, there was no correlation between cord adiponectin levels and maternal body mass index, cord leptin, or insulin levels. Cord adiponectin levels were significantly higher compared with maternal levels at birth (61.1 +/- 19.0 vs. 17.6 +/- 4.9 microg/ml; P < 0.001; n = 17), and no correlation was found between cord and maternal adiponectin levels. There were no significant differences between adiponectin levels at birth and 4 d postpartum (61.1 +/- 19.0 vs. 63.8 +/- 22.0 microg/ml; n = 17). These findings indicate that adiponectin in cord blood is derived from fetal and not from placental or maternal tissues. The high adiponectin levels in newborns compared with adults may be due to lack of negative feedback on adiponectin production resulting from lack of adipocyte hypertrophy, low percentage of body fat, or a different distribution of fat depots in the newborns.

Ageing and adrenal cortical function

Ageing is associated with changes in the secretion of adrenal cortical steroids. In the elderly, cortisol secretion increases after stimulation, while the secretion of dehydroepiandrosterone (DHEA) decreases. Each of these hormones influences the age-related processes of energy metabolism, fat depot distribution, immune function and neurodegeneration. In animals the effects of adrenal steroids are dramatic and easily measured. In humans the effects are more subtle. This review summarizes these actions and emphasizes the differences of dosages used in various experimental designs. It is concluded that adrenal hormones may play a significant role in human ageing, but research is hindered because the molecular pathways of DHEA action are not known.

Correlated responses in development and distribution of fat depots in mice selected for body composition traits

Development of adipose tissue in five depots was investigated in mice selected for high or low 12-week epididymal fat pad weight as a percentage of body weight (HF and LF lines), or high or low 12-week hind carcass weight as a percentage of body weight (HL and LL lines). An unselected control line (RC) was maintained. Hind carcass (HC) and fat pads from subcutaneous hindlimb, subcutaneous forelimb, gonads, kidneys and mesentery were dissected and weighed at 4, 6, 9, 12 or 15 weeks of age. Generally, body weight (BW), daily gain (DG), feed intake (FI), feed efficiency (FE) and feed intake/metabolic body weight (FC) were higher (P≤0.05) in HF than in LF, and in LL than in HL. HF had more fat (as a percentage of BW) than LF in all depots (P≲-0.01), and asymmetry (P≤0.01) was detected for gonadal fat. LL consistently had a higher (P≤0.01) fat percentage than HL, and asymmetry (P≤0.01) was observed for perirenal fat. At age of selection, ranking of fat depot weights as a percentage of total fat depot weight was not changed by selection; however, gonadal fat accounted for more of the total fat in HF and LL compared with RC, while the opposite was found in LF and HL. HC percentage was higher (P≤0.01) in HL than LL, and higher (P≤0.01) in LF than HF. Growth rate of each fat depot relative to BW was not affected by selection. These results demonstrated that selection for proportion of fat in one depot or for HC percentage changed fat percentage in other depots. However, the rate of fat deposition in each depot relative to body weight gain was not altered.

The effects of genotype, sex and feeding regimen on pig carcass development: 2. Tissue weight distribution and fat partition between depots

SUMMARYDissection data for 1006 carcasses taken from the first 2 years of the Meat and Livestock Commission's (MLC) Commercial Pig Evaluation (CPE) were used to examine the growth of tissue weights in joints relative to the corresponding total tissue weight in carcass, and the growth of fat depots relative to total fat over the carcass weight range, 46–92 kg. Growth relationships were examined using a linear allometric model. Differences in tissue weight distribution between genotypes (pigs from different companies in CPE), sexes (barrows and gilts) and feeding regimens (restricted and ad libitum feeding) were examined at constant lean, bone or fat weight as appropriate, common allometric regression slopes being assumed.Lean and bone showed the same pattern of development. Relative growth was lowest in the proximal limb joints (ham and hand) increasing inwards to the joints of the back. With minor differences, the same pattern was found for subcutaneous fat and intermuscular fat. Fat depots differed considerably in their growth relative to total fat: intermuscular fat grew more slowly (allometric growth coefficient, b = 0·87), subcutaneous fat at the same rate and perinephric and retroperitoneal fat (flare fat) more rapidly (b = 1·24).Significant differences were recorded between genotypes in lean distribution and in the distribution of fat depots. However, the differences were small and of little commercial importance. There were also differences in fat partition between genotypes, flare fat being the most variable depot.Sex and feeding regimen also influenced tissue distribution and fat partition.The results are discussed in relation to the robustness of regression equations for predicting overall carcass composition from subcutaneous fat measurements and sample joint dissections.