Cold has been a long-term survival challenge in the evolutionary process of mammals. In response to cold stress, in addition to brown adipose tissue (BAT) dissipating energy as heat through glucose and lipid oxidation to maintain body temperature, cold stimulation can strongly activate thermogenesis and energy expenditure in beige fat cells, which are widely distributed in the subcutaneous layer. However, the effects of cold stimulation on other tissues and systemic lipid metabolism remain unclear. Our previous research indicated that, under cold stress, BAT not only produces heat but also secretes numerous exosomes to mediate BAT-liver crosstalk. Whether subcutaneous fat has a similar mechanism is still unknown. Therefore, this study aimed to investigate the alterations in lipid metabolism across various tissues under cold exposure and to explore whether subcutaneous fat regulates systemic glucose and lipid metabolism via exosomes, thereby elucidating the regulatory mechanisms of lipid metabolism homeostasis under physiological stress. RT-qPCR, Western blot, and H&E staining methods were used to investigate the physiological changes in lipid metabolism in the serum, liver, epididymal white adipose tissue, and subcutaneous fat of mice under cold stimulation. The results revealed that cold exposure significantly enhanced the thermogenic activity of subcutaneous adipose tissue and markedly increased exosome secretion. These exosomes were efficiently taken up by hepatocytes, where they profoundly influenced hepatic lipid metabolism, as evidenced by alterations in the expression levels of key genes involved in lipid synthesis and catabolism pathways. This study has unveiled a novel mechanism by which subcutaneous fat regulates lipid metabolism through exosome secretion under cold stimulation, providing new insights into the systemic regulatory role of beige adipocytes under cold stress and offering a theoretical basis for the development of new therapeutic strategies for obesity and metabolic diseases.
Animals ; Lipid Metabolism/physiology* ; Mice ; Exosomes/metabolism* ; Cold Temperature ; Subcutaneous Fat/physiology* ; Thermogenesis/physiology* ; Adipose Tissue, Brown/metabolism* ; Male

Obesity is a worldwide health problem. An imbalance in energy metabolism is an important cause of obesity and related metabolic diseases. Our previous studies showed that inhibition of miR-429 increased the protein level of uncoupling protein 1 (UCP1) in beige adipocytes; however, whether local inhibition of miR-429 in subcutaneous adipose tissue affects diet-induced obesity and related metabolic disorders remains unclear. The aim of this study was to investigate the effect of local overexpression of miR-429 sponge in subcutaneous adipose tissue on obesity and related metabolic disorders. The control adeno-associated virus (AAV) or AAV expressing the miR-429 sponge was injected into mouse inguinal white adipose tissue. Seven days later, the mice were fed a high-fat diet for 10 weeks to induce obesity. The effects of the miR-429 sponge on body weight, adipose tissue weight, plasma glucose and lipid levels, and hepatic lipid content were explored. The results showed that the overexpression of miR-429 sponge in subcutaneous white adipose tissue reduced body weight and fat mass, decreased fasting blood glucose and plasma cholesterol levels, improved glucose tolerance, and alleviated hepatic lipid deposition in mice. Mechanistic investigation showed that the inhibition of miR-429 significantly upregulated the expression of UCP1 in adipocytes and adipose tissue. These results suggest that local inhibition of miR-429 in subcutaneous white adipose tissue ameliorates obesity and related metabolic disorders potentially by upregulating UCP1, and miR-429 is a potential therapeutic target for the treatment of obesity and related metabolic disorders.
Animals ; MicroRNAs/physiology* ; Obesity/metabolism* ; Mice ; Adipose Tissue, White/metabolism* ; Metabolic Diseases ; Subcutaneous Fat/metabolism* ; Male ; Uncoupling Protein 1/metabolism* ; Diet, High-Fat ; Mice, Inbred C57BL

OBJECTIVETo investigate the correlation between the lumbar bone marrow fat and abdominal fat.

METHODSA total of 68 individuals (32 men and 36 women, aged 21-74 years with a median of 49.5 years) were included in this study. All the subjects underwent spectroscopic examination of the third lumber vertebra with the single voxel method on a 1.5T MR scanner to measure the fat fraction (FF%). Quantitative CT was also performed for measurement of the abdomen subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). The measurements were compared between subjects aged ≥50 years and those below 50 years, respectively,in male or female subjects.

RESULTSIn male subjects, BMI, FF%, VAT or SAT showed no significant differences between the two age groups (P>0.05), and FF% was not correlated with BMI, VAT or SAT (r=0.109, 0.034, 0.066, respectively; P>0.05). In the female subjects, BMI, FF%, VAT and SAT differed significantly between the two age groups (P<0.05), and in ≥50 years group, FF% showed a positive correlation with VAT (r=0.499, P<0.05) but was not correlated with SAT (r=0.221, P>0.05); in<50 years group, FF% was not correlated with VAT or SAT (r=0.076, -0.067, respectively; P>0.05).

CONCLUSIONFF% is positively correlated with VAT in female subjects aged beyond 50 years, but is not correlated with VAT or SAT in male subjects or in younger female subjects.

Adiposity ; Adult ; Aged ; Bone Marrow ; physiology ; Female ; Humans ; Intra-Abdominal Fat ; physiology ; Lumbosacral Region ; Male ; Middle Aged ; Prospective Studies ; Spine ; Subcutaneous Fat, Abdominal ; physiology ; Young Adult

OBJECTIVETo investigate the effect of immunization with prokaryotically expressed recombinant fusion protein of extracellular near-transmembrane domain of Tibet minipig leptin receptor (OBR) on fat deposition in SD rats.

METHODSA pair of specific primers containing BamHI and HindIII restriction enzyme sites was designed to amplify the extracellular near-transmembrane domain (1705-2364 bp) of Tibet minipig OBR gene. After digestion, the amplified fragment was inserted into the plasmid pRSETA between BamHI and HindIII sites. The recombinant plasmid was transformed and expressed in E.coli BL21(DE3) and the product was analyzed by SDS-PAGE and Western blotting. SD rats were immunized with the fusion protein, and the changes in body weight, feed intake, body length, Lee's index, percentage of abdominal fat, liver fat deposition and subcutaneous fat deposition were assessed.

RESULTSThe recombinant fusion protein obtained (about 27.6 kD) was expressed in E.coli induced by IPTG and identified by SDS-PAGE and Western blotting. The rats immunized with the fusion protein showed no significant changes in body weight, body length, Lee's index, percentage of abdominal fat or liver fat deposition as compared with the control rats. Nevertheless, the immunization caused significantly increased feed intake and significantly decreased volume of subcutaneous fat cells.

CONCLUSIONImmunization with the fusion protein of extracellular near-transmembrane domain of Tibet minipig OBR can promote feed intake and suppress subcutaneous fat deposition in SD rats.

Adiposity ; drug effects ; Animals ; Base Sequence ; Female ; Gene Expression ; Genetic Vectors ; Obesity ; Plasmids ; Rats ; Rats, Sprague-Dawley ; Receptors, Leptin ; administration & dosage ; genetics ; Recombinant Fusion Proteins ; administration & dosage ; genetics ; Subcutaneous Fat ; physiology ; Swine ; Swine, Miniature

Computed tomography (CT) exams were conducted to determine the distribution of abdominal fat identified based on the CT number measured in Hounsfield Units (HU) and to measure the volume of the abdominal visceral and subcutaneous fat in minipigs. The relationship between the CT-based fat volumes of several vertebral levels and the entire abdomen and anthropometric data including the sagittal abdominal diameter and waist circumference were evaluated. Moreover, the total fat volumes at the T11, T13, L3, and L5 levels were compared with the total fat volume of the entire abdomen to define the landmark of abdominal fat distribution. Using a single-detector CT, six 6-month-old male minipigs were scanned under general anesthesia. Three radiologists then assessed the HU value of visceral and subcutaneous abdominal fat by drawing the region of interest manually at the T11, T13, L1, L3, and L5 levels. The CT number and abdominal fat determined in this way by the three radiologists was found to be correlated (intra-class coefficient = 0.9). The overall HU ranges for the visceral and subcutaneous fat depots were -147.47 to -83.46 and -131.62 to -90.97, respectively. The total fat volume of the entire abdomen was highly correlated with the volume of abdominal fat at the T13 level (r = 0.97, p < 0.0001). These findings demonstrate that the volume of abdominal adipose tissue measured at the T13 level using CT is a strong and reliable predictor of total abdominal adipose volume.
Animals ; *Body Composition ; Male ; Subcutaneous Fat, Abdominal/*radiography ; Swine ; Swine, Miniature/growth & development/*physiology ; Tomography, X-Ray Computed/*veterinary

People with upper body or visceral obesity have a much higher risk of morbidity and mortality from obesity-related metabolic disorders than those with lower body obesity. In an attempt to develop therapeutic strategies targeting visceral obesity, depot- specific differences in the expression of genes in omental and subcutaneous adipose tissues were investigated by DNA array technology, and their roles in adipocyte differentiation were further examined. We found that levels of metallothionein-II (MT-II) mRNA and protein expression were higher in omental than in subcutaneous adipose tissues. The study demonstrates that MT-II may play an important role in adipocyte differentiation of 3T3L1 preadipocytes, and that N-acetylcysteine (NAC) inhibits the adipocyte differentiation of 3T3L1 cells by repressing MT-II in a time- and dose-dependent manner. Furthermore, the intraperitoneal administration of NAC to rats and mice resulted in a reduction of body weights, and a marked reduction in visceral fat tissues. These results suggest that MT-II plays important roles in adipogenesis, and that NAC may be useful as an anti-obesity drug or supplement.
Viscera/drug effects/metabolism ; Time Factors ; Subcutaneous Fat/drug effects ; Rats, Sprague-Dawley ; Rats ; Middle Aged ; Mice, Inbred C57BL ; Mice ; Metallothionein/*genetics/metabolism/physiology ; Male ; Humans ; Female ; Down-Regulation/drug effects/genetics ; Dose-Response Relationship, Drug ; Cell Differentiation/drug effects ; Body Weight/drug effects ; Anti-Obesity Agents/*pharmacology ; Animals ; Aged ; Adipose Tissue/cytology/drug effects/metabolism ; Adipocytes/cytology/drug effects/metabolism ; Acetylcysteine/*pharmacology ; 3T3-L1 Cells