Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss

Karczewska-Kupczewska, Monika; Nikołajuk, Agnieszka; Majewski, Radosław; Filarski, Remigiusz; Stefanowicz, Magdalena; Matulewicz, Natalia; Strączkowski, Marek

doi:10.1530/ec-19-0507

Cited by 14 publications

(6 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 7 In that study, lipase activity was indirectly correlated with BMI. 7 Cidea, a lipolysis inhibitor, 28 was reportedly elevated after weight loss due to cancer, diet, or bariatric surgery, 29 , 30 , 31 , 32 which may be a compensatory mechanism to balance increased lipolysis during weight loss. It will be important for future studies to determine the association of lipolysis markers like FFA, Cidea, and lipase enzymes with clinical markers like survival, tolerance to therapy, hospitalizations, and future weight loss, to determine their clinical relevance and potential as biomarkers for cancer‐associated weight loss.…”

Section: Discussionmentioning

confidence: 99%

Whole‐body and adipose tissue metabolic phenotype in cancer patients

Anderson

Lee

et al. 2022

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

Background Altered adipose tissue (AT) metabolism in cancer‐associated weight loss via inflammation, lipolysis, and white adipose tissue (WAT) browning is primarily implicated from rodent models; their contribution to AT wasting in cancer patients is unclear. Methods Energy expenditure (EE), plasma, and abdominal subcutaneous WAT were obtained from men (aged 65 ± 8 years) with cancer, with (CWL, n = 27) or without (CWS, n = 47) weight loss, and weight‐stable non‐cancer patients (CON, n = 26). Clinical images were assessed for adipose and muscle area while plasma and WAT were assessed for inflammatory, lipolytic, and browning markers. Results CWL displayed smaller subcutaneous AT (SAT; P = 0.05) and visceral AT (VAT; P = 0.034) than CWS, and displayed higher circulating interleukin (IL)‐6 (P = 0.01) and WAT transcript levels of IL‐6 (P = 0.029), IL‐1β (P = 0.042), adipose triglyceride lipase (P = 0.026), and browning markers (Dio2, P = 0.03; PGC‐1a, P = 0.016) than CWS and CON. There was no difference across groups in absolute REE (P = 0.061), %predicted REE (P = 0.18), circulating free fatty acids (FFA, P = 0.13) or parathyroid hormone‐related peptide (PTHrP; P = 0.88), or WAT protein expression of inflammation (IL‐6, P = 0.51; IL‐1β, P = 0.29; monocyte chemoattractant protein‐1, P = 0.23) or WAT protein or gene expression of browning (uncoupling protein‐1, UCP‐1; P = 0.13, UCP‐1, P = 0.14). In patients with cancer, FFA was moderately correlated with WAT hormone‐sensitive lipase transcript (r = 0.38, P = 0.018, n = 39); circulating cytokines were not correlated with expression of WAT inflammatory markers and circulating PTHrP was not correlated with expression of WAT browning markers. In multivariate regression using cancer patients only, body mass index (BMI) directly predicted SAT (N = 25, R2 = 0.72, P < 0.001), VAT (N = 28, R2 = 0.64, P < 0.001), and absolute REE (N = 22, R2 = 0.43, P = 0.001), while BMI and WAT UCP‐1 protein were indirectly associated with %predicted REE (N = 22, R2 = 0.45, P = 0.02), and FFA was indirectly associated with RQ (N = 22, R2 = 0.52, P < 0.001). Conclusions Cancer‐related weight loss was associated with elevated circulating IL‐6 and elevations in some WAT inflammatory, lipolytic and browning marker transcripts. BMI, not weight loss, was associated with increased energy expenditure. The contribution of inflammation and lipolysis, and lack thereof for WAT browning, will need to be clarified in other tumour types to increase generalizability. Future studies should consider variability in fat mass when exploring the relationship between cancer and adipose metabolism and should observe the trajectory of lipolysis and energy expenditure over time to establish the clinical significance of these associations and to inform more mechanistic interpretation of causation.

show abstract

Section: Discussionmentioning

confidence: 99%

Whole‐body and adipose tissue metabolic phenotype in cancer patients

Anderson

Lee

et al. 2022

J cachexia sarcopenia muscle

View full text Add to dashboard Cite

show abstract

“…Although obesity‐related mechanisms are often examined with respect to attained weight, they can also be influenced by short‐term weight changes. Thus, short‐term weight gain can be associated with increased leptin, pro‐inflammatory markers and insulin resistance, 14,15 while weight loss can be associated with lower leptin, lower circulating oestrogens and improved insulin sensitivity 15‐17 . Nevertheless, the overall effect of short‐term weight change is not always predictable and can differ according to baseline weight.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, shortterm weight gain can be associated with increased leptin, proinflammatory markers and insulin resistance, 14,15 while weight loss can be associated with lower leptin, lower circulating oestrogens and improved insulin sensitivity. [15][16][17] Nevertheless, the overall effect of short-term weight change is not always predictable and can differ according to baseline weight. For example, in normal-weight individuals, high leptin resulting from moderate short-term weight gain induces adiponectin expression, while in individuals with established obesity, leptin signalling is impaired and hinders a concomitant adiponectin increase.…”

Section: Discussionmentioning

confidence: 99%

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Christakoudi

Pagoni

Ferrari

et al. 2020

Intl Journal of Cancer

View full text Add to dashboard Cite

Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow‐up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05‐1.23). Compared to stable weight (±0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01‐1.96), postmenopausal breast (HR = 1.08; 1.00‐1.16) and thyroid (HR = 1.40; 1.04‐1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity‐related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06‐1.33), ovary (HR = 1.40; 1.04‐1.91), corpus uteri (HR = 1.42; 1.06‐1.91), kidney (HR = 1.80; 1.20‐2.68) and pancreas in men (HR = 1.81; 1.11‐2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23‐0.69) and colon (HR = 0.69; 0.52‐0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.

show abstract

“…Comparative gene identification 58 (CGI58) is another cofactor for PLIN1 which is bounded with PLIN1 and inhibit the lipolysis via lipase enzymes but after Protein Kinase A activation PLIN1 and other perilipins phosphorylation happened and translocate the HSL into lipid droplets and CGI58 detach from phosphorylated perilipins and bound with ATGL as an activator increase the directly lipolysis rate [84][85][86][87]. Another side G0/G1 gene deactivate the activity of ATGL and reduce the lipolysis [88,89]. However, CGI58 is important regulator of lipolysis process using a binding site on ATGL and other Perilipins like PLIN1, PLIN2 and PLIN5 surface protein of lipid droplets.…”

Section: Mechanistic Approach Of Perilipins For Fat Regulationmentioning

confidence: 99%

Lipid droplets associated perilipins protein insights into finding a therapeutic target approach to cure non-alcoholic fatty liver disease (NAFLD)

Sharma

2022

Futur J Pharm Sci

View full text Add to dashboard Cite

Background Non-alcoholic fatty liver disease (NAFLD) is now the most common form of chronic liver disease in the world, and it’s linked to a slew of other risk factors including diabetes, obesity, dysbiosis and inflammatory bowel disease. More than 30 years ago, a patient was diagnosed with fatty liver with excessive fat accumulation in hepatocytes, a disorder known as hepatosteatosis. There will be no promising therapeutic medicines available from 1980 to 2021 which can reverse the fatty liver to normal liver state. In this review, we highlighted on lipid droplet associated protein which play a major role in accumulation of fat in liver cells and how these cellular pathway could be a promising therapeutic approach to treat the fatty liver disease. Main body Over the last few decades, Western countries follow a high-fat diet and change their lifestyle pattern due to certain metabolic disorders prevalence rate is very high all over the world. NAFLD is a major health issue and burden globally nowadays. Researchers are trying to find out the potential therapeutic target to combat the disease. The exact pathophysiology of the disease is still unclear. In the present decades. There is no Food and Drug Administration approved drugs are available to reverse the chronic condition of the disease. Based on literature survey, lipid droplets and their associated protein like perilipins play an eminent role in body fat regulation. In this review, we explain all types of perilipins such as perilipin1-5 (PLIN1-5) and their role in the pathogenesis of fatty liver which will be helpful to find the novel pharmacological target to treat the fatty liver. Conclusion In this review, majorly focussed on how fat is get deposited into hepatocytes follow the cellular signalling involved during lipid droplet biogenesis and leads to NAFLD. However, up to date still there mechanism of action is unclear. In this review, we hypothesized that lipid droplets associated proteins like perilipins could be better pharmacological target to reverse the chronic stage of fatty liver disease and how these lipid droplets associated proteins hide a clue to maintain the normal lipid homeostasis in the human body.

show abstract

Changes in adipose tissue lipolysis gene expression and insulin sensitivity after weight loss

Cited by 14 publications

References 48 publications

Whole‐body and adipose tissue metabolic phenotype in cancer patients

Whole‐body and adipose tissue metabolic phenotype in cancer patients

Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Lipid droplets associated perilipins protein insights into finding a therapeutic target approach to cure non-alcoholic fatty liver disease (NAFLD)

Contact Info

Product

Resources

About