bims-mimead 2026-05-24 papers

Issue of 2026–05–24
four papers selected by
Rachel M. Handy, University of Guelph

Physiol Rep. 2026 May;14(10): e70925

Postbiotics lower adipose tissue MHCII inflammation and blood glucose in obese mice, dependent on sex.

Angela M Schmidt, Amee M Scribe, Nicole G Barra, Brittany M Duggan, Han Fang, Dana Kukje Zada, Jonathan D Schertzer.

Obesity is characterized by compartmentalized inflammation in metabolic tissues and risk of dysglycemia, which can be influenced by bacterial components and metabolites (i.e., postbiotics). The postbiotic muramyl dipeptide (MDP) improves blood glucose control in obese male, but not female, mice. The immune response linking MDP to blood glucose was not known. We hypothesized that MDP lowers class II major histocompatibility complex (MHCII) immunity in a sex- and tissue-dependent manner, and that lower MHCII immunity in adipose tissue correlates with improved blood glucose control in obese male mice. We showed that diet-induced obesity increased the transcript levels of multiple components of MHCII immunity in adipose tissue of obese male and female mice, which positively correlated with increased fasting blood glucose. We found that 5 weeks of MDP injections lowered transcript levels of MHCII surface expression and T-cell activation markers in adipose tissue of obese male mice, with minimal changes in the liver or in obese female mice. Lower MHCII inflammatory markers in adipose tissue positively correlated with improved glucose tolerance, but not fasting blood glucose, in obese male mice. Therefore, postbiotic-induced sex-specific improvements blood glucose control are linked to lower transcription of MHCII inflammation in adipose tissue of obese male mice.

Keywords: biological sex; blood glucose; inflammation; obesity; postbiotics

DOI: https://doi.org/10.14814/phy2.70925

Mol Med. 2026 May 18.

Gdf15 expression in thermogenic adipocytes regulates diet-induced weight gain in a sex-dependent manner.

Jayashree Jena, Ayushi Sood, Joshua Peterson, Luis Miguel García-Peña, Eric T Weatherford, Pritesh Patel, Shelly Roitershtein, David A Smith, Vamsi Challa, Randy J Seeley, Renata O Pereira.

BACKGROUND: Growth differentiation factor 15 (GDF15) is a stress-induced cytokine known to bind to its endogenous receptor GDNF-family α-like (GFRAL) in the hindbrain, thereby modulating energy homeostasis. In response to prolonged high-fat diet (HFD) feeding, Gdf15 expression is induced in various tissues, including liver and brown adipose tissue (BAT), leading to increased GDF15 serum levels. Although the liver is the primary source of circulating GDF15 during diet-induced obesity (DIO), other tissues are also required. We investigated whether BAT contributes to GDF15 circulating levels and if GDF15 induction in BAT regulates systemic metabolism during DIO.
METHODS: We generated mice with selective Gdf15 deletion in thermogenic adipocytes (KO) and subjected them to 12 weeks of HFD feeding to determine the role of BAT-derived GDF15 on systemic metabolic homeostasis in both male and female mice.
RESULTS: Unexpectedely, despite no changes in GDF15 serum levels in mice fed ad-libitum regardless of sex or genotype, female KO mice were resistant to DIO, had increased energy expenditure and improved mitochondrial fatty acid oxidation in BAT, which was prevented by ovariectomy. Conversely, male KO mice had increased body weight and adiposity upon HFD feeding, along with reduced respiratory capacity in BAT mitchondria, and increased markers of fibro-inflammation.
CONCLUSIONS: Together, our data reveal GDF15 induction in BAT is required to regulate weight gain in mice in a sex-dependent manner. Our results also suggest female sex hormones contribute to increase energy expenditure in female KO mice promoting leanness. Our study underscore the importance of rigorously addressing sex differences in GDF15 biology and pharmacology and suggests GDF15 might exert effects on energy balance and adiposity that are independent of signaling through GFRAL.

Keywords: Brown adipose tissue; GDF15; Obesity; Sex dimorphism

DOI: https://doi.org/10.1186/s10020-026-01505-5

FASEB J. 2026 May 31. 40(10): e71941

OPA1 in MC4R Neurons Regulates Dietary Fat Intake and Body Weight in Mice.

Shigenobu Matsumura, Mizuki Fujiwara, Soyoka Horie, Miona Marutani, Eri Nousou, Nanase Iki, Yuka Yamato, Yui Otonashi, Tsutomu Sasaki, Mina Fujitani, Teppei Fujikawa.

Melanocortin 4 receptor (MC4R) neurons in the hypothalamus regulate appetite and energy balance, and mitochondrial dynamics are important for neuronal function. However, how dietary fat intake affects mitochondrial regulation in the hypothalamus has not been fully clarified. Here we examined the effects of soybean oil intake on hypothalamic mitochondrial gene expression and generated MC4R neuron-specific mitochondrial fusion factor OPA1 (Optic atrophy-1) knockout mice. Voluntary ingestion of soybean oil increased hypothalamic OPA1 expression in wild-type male mice but not in female mice. In contrast, loss of OPA1 in MC4R neurons led to elevated soybean oil consumption and progressive obesity, with a more pronounced obesity phenotype in females. MC4R agonist administration suppressed food intake, but this effect was attenuated specifically in female knockout mice. Together, these results suggest that OPA1 in MC4R neurons is involved in the response to dietary fat intake and contributes to the control of feeding and body weight, with clear differences between males and females. This study provides new insight into how mitochondrial function in the hypothalamus is linked to energy metabolism under conditions of dietary fat intake.

Keywords: MC4R neurons; OPA1 deficiency; energy metabolism; mitochondrial dynamics

DOI: https://doi.org/10.1096/fj.202600452R

Am J Physiol Endocrinol Metab. 2026 May 21.

Heterogeneity in postprandial glucose-insulin and triacylglycerol dynamics and associations with plasma metabolome and body composition in obesity.

Nikolai B Aunbakk, Siv Kjølsrud Bøhn, Johnny Laupsa-Borge, Cathrine Sommersten, Adrian McCann, Gülen Arslan Lied, Ottar Nygård, Jutta Dierkes, Gunnar Mellgren, Simon N Dankel, Kathrine Frey Frøslie.

We are only beginning to understand the extent and reasons for the individual variation in postprandial response dynamics in key hormones and metabolites such as insulin, glucose and triacylglycerols (TAGs). More nuanced statistical approaches for postprandial curve analyses, coupled with phenotyping of curve-associated factors, may help uncover the underlying physiology and possible associations with disease risk. In a clinical trial of 190 adults (90 males, 100 females) with abdominal obesity (age: 21-56 BMI: 26-54), we used functional principal component analysis (FPCA) to examine postprandial serum glucose, C-peptide, and TAGs after a 4-hour standardized mixed meal test. Correlations were explored between identified curve patterns and more than 100 anthropometric and fasting biochemistry traits. Postprandial curve levels, peaks, and dips varied substantially. While the primary patterns in postprandial glucose, C-peptide, and TAGs uncovered by FPCA corresponded with area under the curve (AUC), the presence and timing of curve peaks and dips was uncorrelated with AUC. Males had higher postprandial levels and larger variation than females. Over 40% of the participants had non-synchronized postprandial glucose and C-peptide curves. A postprandial phenotype characterized by elevated and delayed postprandial peaks in glucose and C-peptide, and a high postprandial TAG level and peak, was strongly associated with multiple blood biomarkers and anthropometric traits linked to insulin resistance and liver pathologies (correlation range: -0.49, 0.63). While our findings support the general usefulness of postprandial AUC, FPCA provided detailed insight into individual postprandial glucose and insulin dynamics which may inform improved diagnostics and personalized dietary advice.

Keywords: Functional Principal Component Analysis; Glucose-Insulin dynamics; Obesity; Postprandial responses; Postprandial triacylglycerol metabolism

DOI: https://doi.org/10.1152/ajpendo.00499.2025