Effects of co-occurring Wolbachia and Spiroplasma endosymbionts on the Drosophila immune response against insect pathogenic and non-pathogenic bacteria.

BACKGROUND: Symbiotic interactions between microbes and animals are common in nature. Symbiotic organisms are particularly common in insects and, in some cases, they may protect their hosts from pathogenic infections. Wolbachia and Spiroplasma endosymbionts naturally inhabit various insects including Drosophila melanogaster fruit flies. Therefore, this symbiotic association is considered an excellent model to investigate whether endosymbiotic bacteria participate in host immune processes against certain pathogens. Here we have investigated whether the presence of Wolbachia alone or together with Spiroplasma endosymbionts in D. melanogaster adult flies affects the immune response against the virulent insect pathogen Photorhabdus luminescens and against non-pathogenic Escherichia coli bacteria. RESULTS: We found that D. melanogaster flies carrying no endosymbionts, those carrying both Wolbachia and Spiroplasma, and those containing Wolbachia only had similar survival rates after infection with P. luminescens or Escherichia coli bacteria. However, flies carrying both endosymbionts or Wolbachia only contained higher numbers of E. coli cells at early time-points post infection than flies without endosymbiotic bacteria. Interestingly, flies containing Wolbachia only had lower titers of this endosymbiont upon infection with the pathogen P. luminescens than uninfected flies of the same strain. We further found that the presence of Wolbachia and Spiroplasma in D. melanogaster up-regulated certain immune-related genes upon infection with P. luminescens or E. coli bacteria, but it failed to alter the phagocytic ability of the flies toward E. coli inactive bioparticles. CONCLUSION: Our results suggest that the presence of Wolbachia and Spiroplasma in D. melanogaster can modulate immune signaling against infection by certain insect pathogenic and non-pathogenic bacteria. Results from such studies are important for understanding the molecular basis of the interactions between endosymbiotic bacteria of insects and exogenous microbes.

Lipid profiles and hypertriglyceridemia among transgender and gender diverse adults on gender-affirming hormone therapy.

BACKGROUND: The effects of gender-affirming hormone therapy on lipid profiles among transgender adults have been inconsistent and incompletely characterized. OBJECTIVE: To longitudinally assess changes to lipid profiles following hormone therapy and to establish prevalence rates of hyperlipidemia/low HDL-cholesterol. METHODS: This longitudinal study followed lipid profiles of 366 transgender and gender-diverse adult patients (170 transfeminine and 196 transmasculine; mean age, 28 years) in Washington DC USA. Lipid profiles were measured at baseline and at multiple follow-up clinical visits up to 57 months after the initiation of hormone therapy. RESULTS: Within 2-10 months of starting gender-affirming hormone therapy, mean levels of HDL-cholesterol decreased by 16% in transmasculine individuals and increased by 11% in transfeminine individuals. Over the study, mean triglyceride levels increased by 26-37% in the transmasculine group. Over the study, the prevalence of moderate hypertriglyceridemia (175-499 mg/dL) ranged from 11 to 32% in the transfeminine group and 6-19% in the transmasculine group. Severe hypertriglyceridemia (≥500 mg/dL) was only observed in one individual. On hormone therapy, 24-30% of the transfeminine group had a HDL-cholesterol < 50 mg/dL and 16-24% of the transmasculine group had a HDL-cholesterol < 40 mg/dL. LDL-cholesterol levels ≥160 mg/dL were rare among both groups. CONCLUSIONS: In a gender-diverse population on hormone therapy, low HDL-cholesterol and moderate hypertriglyceridemia were relatively common. HDL-cholesterol decreased with testosterone therapy and increased with a combination of oral estrogen and spironolactone. Testosterone use was associated with an increase in triglycerides. Our data support the recommendation to routinely monitor lipid profiles in gender-diverse patients on GAHT.

Blood Pressure Effects of Gender-Affirming Hormone Therapy in Transgender and Gender-Diverse Adults.

[Figure: see text].

GPRC6a is not required for the effects of a high-protein diet on body weight in mice.

OBJECTIVE: The G-protein coupled receptor family C group 6 member A (GPRC6A) is activated by proteinogenic amino acids and may sense amino acids in the gastrointestinal tract and the brain. The study investigated whether GPRC6A was necessary for the effects of low- and high-protein diets on body weight and food intake in mice. METHODS: The role of GPRC6A in mediating the effects of a low-protein diet on body weight was investigated in GPRC6a knockout (GPRC6a-KO) and wild-type (WT) mice fed a control diet (18% protein) or a low-protein diet (6% protein) for 9 days. The role of GPRC6A in mediating the effects of a high-protein diet on body weight was investigated in GPRC6a-KO and WT mice fed a control diet (18% protein) or a high-protein diet (50% protein) for 5 weeks. RESULTS: A high-protein diet reduced body weight gain and food intake compared with a control diet in both WT and GPRC6a-KO mice. A low-protein diet decreased body weight gain in GPRC6a-KO mice. CONCLUSIONS: GPRC6A was not necessary for the effects of a low- or high-protein diet on body weight and likely does not play a role in protein-induced satiety.