1.
Weight loss did not modify macronutrient specific response of hormones and satiety in overweight and obese people without metabolic disease - results from a clinical trial.
Li, L, Decker, AM, Stobäus, N, Beer, F, Grittner, U, Spranger, J, Mai, K
Clinical nutrition (Edinburgh, Scotland). 2022;(4):948-957
Abstract
BACKGROUND & AIMS Sustained weight loss is highly desirable in obesity. Although the role of incretins in the regulation of body weight is well known, macronutrient specific incretin response and the effects of weight loss on this response have not been investigated before. We aimed to examine GLP-1, GIP, ghrelin, insulin, and satiety response to meals with different macronutrient composition in overweight and obese subjects before and after weight loss. METHODS 32 overweight and obese participants underwent meal tests before and after weight loss intervention. Test meals were designed to be either carbohydrate (CHO), fat (FAT), or protein (PRO) enriched to test macronutrient specific response. Macronutrient specific response of GLP-1, GIP, and ghrelin before and after weight loss were the primary outcome measures. Response of insulin and satiety were predefined secondary endpoints. RESULTS There were macronutrient specific response patterns of GLP-1 (PRO>FAT=CHO), GIP (CHO=FAT>PRO), and insulin (CHO>PRO=FAT). Postprandial decline of ghrelin did not differ between the test meals. Hunger, desire to eat, and prospective food consumption were highest after CHO intake (CHO>PRO=FAT) at baseline. After weight loss, fasting and postprandial GLP-1 and insulin were reduced while concomitant ghrelin levels were increased. However, the macronutrient specific hormonal response pattern did not change after weight loss. While weight loss increased hunger and desire to eat, the macronutrient specific differences were lost after weight reduction. Higher weight loss was associated with a stronger decline of PRO induced GLP-1 response (ρ = 0.45, p = 0.024, n = 27). CONCLUSIONS Both hormones and satiety showed a macronutrient specific response in overweight/obese participants with a possibly favorable role of protein. However, weight loss may cause a partial disruption of this hormone-satiety-connection as macronutrient specific response pattern of satiety scores representing impulse control in particular but not incretins disappeared. TRIAL REGISTRATION NCT02649907. https://clinicaltrials.gov/ct2/show/NCT02649907.
2.
Fetuin-B, a potential link of liver-adipose tissue cross talk during diet-induced weight loss-weight maintenance.
Li, L, Spranger, L, Stobäus, N, Beer, F, Decker, AM, Wernicke, C, Brachs, S, Brachs, M, Spranger, J, Mai, K
Nutrition & diabetes. 2021;(1):31
Abstract
BACKGROUND/OBJECTIVES Numerous hepatokines are involved in inter-organ cross talk regulating tissue-specific insulin sensitivity. Adipose tissue lipolysis represents a crucial element of adipose insulin sensitivity and is substantially involved in long-term body weight regulation after dietary weight loss. Thus, we aimed to analyze the impact of the hepatokine Fetuin-B in the context of weight loss induced short- and long-term modulation of adipose insulin sensitivity. SUBJECTS/METHODS 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before (T-3) and after (T0) a standardized 12-week dietary weight reduction program. Afterward, subjects were randomized to a 12-month lifestyle intervention or a control group. After 12 months (T12) no further intervention was performed until 6 months later (T18) (Maintain-Adults trial). Tissue-specific insulin sensitivity was estimated by HOMA-IR (predominantly liver), ISIClamp (predominantly skeletal muscle), and free fatty acid suppression during hyperinsulinemic-euglycemic clamp (FFASupp) (predominantly adipose tissue). Fetuin-B was measured at all concomitant time points. RESULTS Circulating Fetuin-B levels correlated significantly with estimates of obesity, hepatic steatosis as well as HOMA-IR, ISIClamp, FFASupp at baseline. Fetuin-B decreased during dietary weight loss (4.2 (3.5-4.9) vs. 3.8 (3.2-4.6) µg/ml; p = 2.1 × 10-5). This change was associated with concomitant improvement of HOMA-IR (r = 0.222; p = 0.008) and FFASupp (r = -0.210; p = 0.013), suggesting a particular relationship to hepatic and adipose tissue insulin sensitivity. Weight loss induced improvements of insulin resistance were almost completely preserved until months 12 and 18 and most interestingly, the short and long-term improvement of FFASupp was partially predicted by baseline level of Fetuin-B. CONCLUSIONS Our data suggest that Fetuin-B might be a potential mediator of liver-adipose cross talk involved in short- and long-term regulation of adipose insulin sensitivity, especially in the context of diet-induced weight changes. TRIAL REGISTRATION ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629 , date of registration: February 25, 2009.
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Metabolic impact of weight loss induced reduction of adipose ACE-2 - Potential implication in COVID-19 infections?
Li, L, Spranger, L, Soll, D, Beer, F, Brachs, M, Spranger, J, Mai, K
Metabolism: clinical and experimental. 2020;113:154401
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Obesity is now recognised as a risk factor for increased severity of Covid-19 infections. ACE-2 is a protein that has many functions but also allows Covid-19 into cells and is particularly evident in body tissues, which store fat. It is therefore possible that Covid-19 will target fat-storing tissues in the body. This 12-month randomised control weight-loss intervention study of 143 obese individuals aimed to determine ACE-2 expression and whether it could be modified by weight loss. The results showed that ACE-2 was only present in fat storing tissue and not muscle tissue. Interestingly individuals with pre-diabetes or diabetes had the lowest levels of ACE-2. Weight loss resulted in reduced ACE-2 in fat storing tissue, which resulted in an improvement in markers for diabetes. It was concluded that reduction of ACE-2 in fat storing tissues as a result of weight loss can improve markers for diabetes and could impact the severity of Covid-19 infection. Healthcare professionals could use this study to understand how weight loss in patients with obesity could decrease their risk of severe Covid-19 infection.
Abstract
BACKGROUND & AIMS Angiotensin converting enzyme (ACE)-2 is a modulator of adipose tissue metabolism. However, human data of adipose ACE-2 is rarely available. Considering that, ACE-2 is believed to be the receptor responsible for cell entry of SARS-CoV-2, a better understanding of its regulation is desirable. We therefore characterized the modulation of subcutaneous adipose ACE-2 mRNA expression during weight loss and the impact of ACE-2 expression on weight loss induced short- and long-term improvements of glucose metabolism. METHODS 143 subjects (age > 18; BMI ≥ 27 kg/m2) were analyzed before and after a standardized 12-week dietary weight reduction program. Afterwards subjects were randomized to a 12-month lifestyle intervention or a control group (Maintain-Adults trial). Insulin sensitivity (IS) was estimated by HOMA-IR (as an estimate of liver IS) and ISIClamp (as an estimate of skeletal muscle IS). ACE-2 mRNA expression (ACE-2AT) was measured in subcutaneous adipose tissue before and after weight loss. RESULTS ACE-2AT was not affected by obesity, but was reduced in insulin resistant subjects. Weight loss resulted in a decline of ACE-2AT (29.0 (20.0-47.9) vs. 21.0 (13.0-31.0); p = 1.6 ∗ 10-7). A smaller reduction of ACE-2 AT (ΔACE-2AT) was associated with a larger improvement of ISIClamp (p = 0.013) during weight reduction over 3 months, but not with the extend of weight loss. The degree of changes in insulin resistance were preserved until month 12 and was also predicted by the weight loss induced degree of ΔACE-2AT (p = 0.011). CONCLUSIONS Our data indicate that subcutaneous adipose ACE-2 expression correlates with insulin sensitivity. Weight loss induced decline of subcutaneous adipose ACE-2 expression might affect short- and long-term improvement of myocellular insulin sensitivity, which might be also relevant in the context of ACE-2 downregulation by SARS-CoV-2. TRIAL REGISTRATION ClinicalTrials.gov number: NCT00850629, https://clinicaltrials.gov/ct2/show/NCT00850629, date of registration: February 25, 2009.